Tumor immunity: A brief overview of tumor‑infiltrating immune cells and research advances into tumor‑infiltrating lymphocytes in gynecological malignancies (Review)

Wang,Zi-Tao; Deng,Zhi-Min; Dai,Fang-Fang; Yuan,Meng-Qin; Liu,Shi-Yi; Li,Bing-Shu; Cheng,Yan-Xiang

doi:10.3892/etm.2024.12453

Tumor immunity: A brief overview of tumor‑infiltrating immune cells and research advances into tumor‑infiltrating lymphocytes in gynecological malignancies (Review)

Authors:
- Zi-Tao Wang
- Zhi-Min Deng
- Fang-Fang Dai
- Meng-Qin Yuan
- Shi-Yi Liu
- Bing-Shu Li
- Yan-Xiang Cheng
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Affiliations: Department of Obstetrics and Gynecology, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China, Department of Obstetrics and Gynecology, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China
Published online on: February 26, 2024 https://doi.org/10.3892/etm.2024.12453
Article Number: 166
Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Tumor immunity is a promising topic in the area of cancer therapy. The ‘soil’ function of the tumor microenvironment (TME) for tumor growth has attracted wide attention from scientists. Tumor‑infiltrating immune cells in the TME, especially the tumor‑infiltrating lymphocytes (TILs), serve a key role in cancer. Firstly, relevant literature was searched in the PubMed and Web of Science databases with the following key words: ‘Tumor microenvironment’; ‘TME’; ‘tumor‑infiltrating immunity cells’; ‘gynecologic malignancies’; ‘the adoptive cell therapy (ACT) of TILs’; and ‘TIL‑ACT’ (https://pubmed.ncbi.nlm.nih.gov/). According to the title and abstract of the articles, relevant items were screened out in the preliminary screening. The most relevant selected items were of two types: All kinds of tumor‑infiltrating immune cells; and advanced research on TILs in gynecological malignancies. The results showed that the subsets of TILs were various and complex, while each subpopulation influenced each other and their effects on tumor prognosis were diverse. Moreover, the related research and clinical trials on TILs were mostly concentrated in melanoma and breast cancer, but relatively few focused on gynecological tumors. In conclusion, the present review summarized the biological classification of TILs and the mechanisms of their involvement in the regulation of the immune microenvironment, and subsequently analyzed the development of tumor immunotherapy for TILs. Collectively, the present review provides ideas for the current treatment dilemma of gynecological tumor immune checkpoints, such as adverse reactions, safety, personal specificity and efficacy.

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1	Naito Y, Yoshioka Y, Yamamoto Y and Ochiya T: How cancer cells dictate their microenvironment: Present roles of extracellular vesicles. Cell Mol Life Sci. 74:697–713. 2017.PubMed/NCBI View Article : Google Scholar
2	Maman S and Witz IP: A history of exploring cancer in context. Nat Rev Cancer. 18:359–376. 2018.PubMed/NCBI View Article : Google Scholar
3	Sharma P and Allison JP: Immune checkpoint targeting in cancer therapy: Toward combination strategies with curative potential. Cell. 161:205–214. 2015.PubMed/NCBI View Article : Google Scholar
4	Bejarano L, Jordāo MJC and Joyce JA: Therapeutic targeting of the tumor microenvironment. Cancer Discov. 11:933–959. 2021.PubMed/NCBI View Article : Google Scholar
5	Chung HC, Ros W, Delord JP, Perets R, Italiano A, Shapira-Frommer R, Manzuk L, Piha-Paul SA, Xu L, Zeigenfuss S, et al: Efficacy and safety of pembrolizumab in previously treated advanced cervical cancer: Results from the phase II KEYNOTE-158 Study. J Clin Oncol. 37:1470–1478. 2019.PubMed/NCBI View Article : Google Scholar
6	Koh WJ, Abu-Rustum NR, Bean S, Bradley K, Campos SM, Cho KR, Chon HS, Chu C, Clark R, Cohn D, et al: Cervical Cancer, Version 3.2019, NCCN clinical practice guidelines in oncology. J Natl Compr Canc Netw. 17:64–84. 2019.PubMed/NCBI View Article : Google Scholar
7	Li X, Shao C, Shi Y and Han W: Lessons learned from the blockade of immune checkpoints in cancer immunotherapy. J Hematol Oncol. 11(31)2018.PubMed/NCBI View Article : Google Scholar
8	Matanes E and Gotlieb WH: Immunotherapy of gynecological cancers. Best Pract Res Clin Obstet Gynaecol. 60:97–110. 2019.PubMed/NCBI View Article : Google Scholar
9	Duranti S, Pietragalla A, Daniele G, Nero C, Ciccarone F, Scambia G and Lorusso D: Role of immune checkpoint inhibitors in cervical cancer: From preclinical to clinical data. Cancers (Basel). 13(2089)2021.PubMed/NCBI View Article : Google Scholar
10	Ventriglia J, Paciolla I, Pisano C, Cecere SC, Di Napoli M, Tambaro R, Califano D, Losito S, Scognamiglio G, Setola SV, et al: Immunotherapy in ovarian, endometrial and cervical cancer: State of the art and future perspectives. Cancer Treat Rev. 59:109–116. 2017.PubMed/NCBI View Article : Google Scholar
11	Salgado R, Denkert C, Demaria S, Sirtaine N, Klauschen F, Pruneri G, Wienert S, Van den Eynden G, Baehner FL, Penault-Llorca F, et al: The evaluation of tumor-infiltrating lymphocytes (TILs) in breast cancer: Recommendations by an International TILs Working Group 2014. Ann Oncol. 26:259–271. 2015.PubMed/NCBI View Article : Google Scholar
12	Hanahan D and Weinberg RA: Hallmarks of cancer: The next generation. Cell. 144:646–674. 2011.PubMed/NCBI View Article : Google Scholar
13	Sasada T and Suekane S: Variation of tumor-infiltrating lymphocytes in human cancers: Controversy on clinical significance. Immunotherapy. 3:1235–1251. 2011.PubMed/NCBI View Article : Google Scholar
14	Quail DF and Joyce JA: Microenvironmental regulation of tumor progression and metastasis. Nat Med. 19:1423–1437. 2013.PubMed/NCBI View Article : Google Scholar
15	Murphy KM and Reiner SL: The lineage decisions of helper T cells. Nat Rev Immunol. 2:933–944. 2002.PubMed/NCBI View Article : Google Scholar
16	Szabo SJ, Dighe AS, Gubler U and Murphy KM: Regulation of the interleukin (IL)-12R beta 2 subunit expression in developing T helper 1 (Th1) and Th2 cells. J Exp Med. 185:817–824. 1997.PubMed/NCBI View Article : Google Scholar
17	Xu D, Chan WL, Leung BP, Hunter D, Schulz K, Carter RW, McInnes IB, Robinson JH and Liew FY: Selective expression and functions of interleukin 18 receptor on T helper (Th) type 1 but not Th2 cells. J Exp Med. 188:1485–1492. 1998.PubMed/NCBI View Article : Google Scholar
18	Sallusto F, Lenig D, Mackay CR and Lanzavecchia A: Flexible programs of chemokine receptor expression on human polarized T helper 1 and 2 lymphocytes. J Exp Med. 187:875–883. 1998.PubMed/NCBI View Article : Google Scholar
19	Loetscher P, Uguccioni M, Bordoli L, Baggiolini M, Moser B, Chizzolini C and Dayer JM: CCR5 is characteristic of Th1 lymphocytes. Nature. 391:344–345. 1998.PubMed/NCBI View Article : Google Scholar
20	Austrup F, Vestweber D, Borges E, Löhning M, Bräuer R, Herz U, Renz H, Hallmann R, Scheffold A, Radbruch A and Hamann A: P- and E-selectin mediate recruitment of T-helper-1 but not T-helper-2 cells into inflammed tissues. Nature. 385:81–83. 1997.PubMed/NCBI View Article : Google Scholar
21	Basu A, Ramamoorthi G, Albert G, Gallen C, Beyer A, Snyder C, Koski G, Disis ML, Czerniecki BJ and Kodumudi K: Differentiation and Regulation of TH cells: A balancing Act for cancer immunotherapy. Front Immunol. 12(669474)2021.PubMed/NCBI View Article : Google Scholar
22	Hung K, Hayashi R, Lafond-Walker A, Lowenstein C, Pardoll D and Levitsky H: The Central Role of CD4+ T cells in the antitumor immune response. J Exp Med. 188:2357–2368. 1998.PubMed/NCBI View Article : Google Scholar
23	Kim WS, Shin MK and Shin SJ: MAP1981c, a Putative Nucleic Acid-Binding Protein, Produced by Mycobacterium avium subsp. paratuberculosis, Induces Maturation of Dendritic Cells and Th1-Polarization. Front Cell Infect Microbiol. 8(206)2018.PubMed/NCBI View Article : Google Scholar
24	Bongiorno EK, Garcia SA, Sauma S and Hooper DC: Type 1 immune mechanisms driven by the response to infection with attenuated rabies virus result in changes in the immune bias of the tumor microenvironment and necrosis of mouse GL261 brain tumors. J Immunol. 198:4513–4523. 2017.PubMed/NCBI View Article : Google Scholar
25	Zhu S, Wang X, Wang J, Lin J, Cong Y and Qiao G: CD21^lo/medCD27+ proinflammatory B cells are enriched in breast cancer patients and promote antitumor T cell responses. Exp Cell Res. 361:149–154. 2017.PubMed/NCBI View Article : Google Scholar
26	Zou JY, Su CH, Luo HH, Lei YY, Zeng B, Zhu HS and Chen ZG: Curcumin converts Foxp3+ regulatory T cells to T helper 1 cells in patients with lung cancer. J Cell Biochem. 119:1420–1428. 2018.PubMed/NCBI View Article : Google Scholar
27	Martinez FO, Helming L, Milde R, Varin A, Melgert BN, Draijer C, Thomas B, Fabbri M, Crawshaw A, Ho LP, et al: Genetic programs expressed in resting and IL-4 alternatively activated mouse and human macrophages: Similarities and differences. Blood. 121:e57–e69. 2013.PubMed/NCBI View Article : Google Scholar
28	Badylak SF, Valentin JE, Ravindra AK, McCabe GP and Stewart-Akers AM: Macrophage phenotype as a determinant of biologic scaffold remodeling. Tissue Eng Part A. 14:1835–1842. 2008.PubMed/NCBI View Article : Google Scholar
29	Spiller KL, Anfang RR, Spiller KJ, Ng J, Nakazawa KR, Daulton JW and Vunjak-Novakovic G: The role of macrophage phenotype in vascularization of tissue engineering scaffolds. Biomaterials. 35:4477–4488. 2014.PubMed/NCBI View Article : Google Scholar
30	Gordon S, Plüddemann A and Martinez Estrada F: Macrophage heterogeneity in tissues: Phenotypic diversity and functions. Immunol Rev. 262:36–55. 2014.PubMed/NCBI View Article : Google Scholar
31	Wilson HM: SOCS proteins in macrophage polarization and function. Front Immunol. 5(357)2014.PubMed/NCBI View Article : Google Scholar
32	Stöger JL, Gijbels MJ, van der Velden S, Manca M, van der Loos CM, Biessen EA, Daemen MJ, Lutgens E and de Winther MP: Distribution of macrophage polarization markers in human atherosclerosis. Atherosclerosis. 225:461–468. 2012.PubMed/NCBI View Article : Google Scholar
33	Mills CD: Anatomy of a discovery: m1 and m2 macrophages. Front Immunol. 6(212)2015.PubMed/NCBI View Article : Google Scholar
34	Xiang W, Shi R, Kang X, Zhang X, Chen P, Zhang L, Hou A, Wang R, Zhao Y, Zhao K, et al: Monoacylglycerol lipase regulates cannabinoid receptor 2-dependent macrophage activation and cancer progression. Nat Commun. 9(2574)2018.PubMed/NCBI View Article : Google Scholar
35	Slaney CY, Kershaw MH and Darcy PK: Trafficking of T cells into tumors. Cancer Res. 74:7168–7174. 2014.PubMed/NCBI View Article : Google Scholar
36	Mellor AL and Munn DH: Creating immune privilege: Active local suppression that benefits friends, but protects foes. Nat Rev Immunol. 8:74–80. 2008.PubMed/NCBI View Article : Google Scholar
37	Kaech SM and Cui W: Transcriptional control of effector and memory CD8+ T cell differentiation. Nat Rev Immunol. 12:749–761. 2012.PubMed/NCBI View Article : Google Scholar
38	Wongtrakoongate P: Epigenetic therapy of cancer stem and progenitor cells by targeting DNA methylation machineries. World J Stem Cells. 7:137–148. 2015.PubMed/NCBI View Article : Google Scholar
39	Chen DS and Mellman I: Oncology meets immunology: The cancer-immunity cycle. Immunity. 39:1–10. 2013.PubMed/NCBI View Article : Google Scholar
40	Racioppi L, Nelson ER, Huang W, Mukherjee D, Lawrence SA, Lento W, Masci AM, Jiao Y, Park S, York B, et al: CaMKK2 in myeloid cells is a key regulator of the immune-suppressive microenvironment in breast cancer. Nat Commun. 10(2450)2019.PubMed/NCBI View Article : Google Scholar
41	Wang HL, Hou SY, Li HB, Qiu JP, Bo L and Mao CP: Biological function and mechanism of long noncoding RNAs nuclear-enriched abundant transcript 1 in development of cervical cancer. Chin Med J (Engl). 131:2063–2070. 2018.PubMed/NCBI View Article : Google Scholar
42	Bordon Y: Dendritic cells: Sorting, sorted! Nat Rev Immunol. 16(657)2016.PubMed/NCBI View Article : Google Scholar
43	Hildner K, Edelson BT, Purtha WE, Diamond M, Matsushita H, Kohyama M, Calderon B, Schraml BU, Unanue ER, Diamond MS, et al: Batf3 deficiency reveals a critical role for CD8alpha+ dendritic cells in cytotoxic T cell immunity. Science. 322:1097–1100. 2008.PubMed/NCBI View Article : Google Scholar
44	Gardner A and Ruffell B: Dendritic cells and cancer immunity. Trends Immunol. 37:855–865. 2016.PubMed/NCBI View Article : Google Scholar
45	Swiecki M and Colonna M: The multifaceted biology of plasmacytoid dendritic cells. Nat Rev Immunol. 15:471–485. 2015.PubMed/NCBI View Article : Google Scholar
46	Guilliams M, Dutertre CA, Scott CL, McGovern N, Sichien D, Chakarov S, Van Gassen S, Chen J, Poidinger M, De Prijck S, et al: Unsupervised high-dimensional analysis aligns dendritic cells across tissues and species. Immunity. 45:669–684. 2016.PubMed/NCBI View Article : Google Scholar
47	Ma DY and Clark EA: The role of CD40 and CD154/CD40L in dendritic cells. Semin Immunol. 21:265–272. 2009.PubMed/NCBI View Article : Google Scholar
48	Pasqual G, Chudnovskiy A, Tas JMJ, Agudelo M, Schweitzer LD, Cui A, Hacohen N and Victora GD: Monitoring T cell-dendritic cell interactions in vivo by intercellular enzymatic labelling. Nature. 553:496–500. 2018.PubMed/NCBI View Article : Google Scholar
49	Zanoni I, Tan Y, Di Gioia M, Broggi A, Ruan J, Shi J, Donado CA, Shao F, Wu H, Springstead JR and Kagan JC: An endogenous caspase-11 ligand elicits interleukin-1 release from living dendritic cells. Science. 352:1232–1236. 2016.PubMed/NCBI View Article : Google Scholar
50	Zitvogel L and Kroemer G: CD103 + Dendritic Cells Producing Interleukin-12 in Anticancer Immunosurveillance. Cancer Cell. 26:591–593. 2014.PubMed/NCBI View Article : Google Scholar
51	Liu M, Wang X, Wang L, Ma X, Gong Z, Zhang S and Li Y: Targeting the IDO1 pathway in cancer: From bench to bedside. J Hematol Oncol. 11(100)2018.PubMed/NCBI View Article : Google Scholar
52	Marciscano AE and Anandasabapathy N: The role of dendritic cells in cancer and anti-tumor immunity. Semin Immunol. 52(101481)2021.PubMed/NCBI View Article : Google Scholar
53	Chomarat P, Banchereau J, Davoust J and Palucka AK: IL-6 switches the differentiation of monocytes from dendritic cells to macrophages. Nat Immunol. 1:510–514. 2000.PubMed/NCBI View Article : Google Scholar
54	Kel JM, Girard-Madoux MJ, Reizis B and Clausen BE: TGF-beta is required to maintain the pool of immature Langerhans cells in the epidermis. J Immunol. 185:3248–3255. 2010.PubMed/NCBI View Article : Google Scholar
55	Yang AS and Lattime EC: Tumor-induced interleukin 10 suppresses the ability of splenic dendritic cells to stimulate CD4 and CD8 T-cell responses. Cancer Res. 63:2150–2157. 2003.PubMed/NCBI
56	Shi Y, Yu P, Zeng D, Qian F, Lei X, Zhao Y, Tang B, Hao Y, Luo H, Chen J and Tan Y: Suppression of vascular endothelial growth factor abrogates the immunosuppressive capability of murine gastric cancer cells and elicits antitumor immunity. FEBS J. 281:3882–3893. 2014.PubMed/NCBI View Article : Google Scholar
57	Huang LY, Reis e Sousa C, Itoh Y, Inman J and Scott DE: IL-12 induction by a TH1-inducing adjuvant in vivo: Dendritic cell subsets and regulation by IL-10. J Immunol. 167:1423–1430. 2001.PubMed/NCBI View Article : Google Scholar
58	Oderup C, Cederbom L, Makowska A, Cilio CM and Ivars F: Cytotoxic T lymphocyte antigen-4-dependent down-modulation of costimulatory molecules on dendritic cells in CD4+ CD25+ regulatory T-cell-mediated suppression. Immunology. 118:240–249. 2006.PubMed/NCBI View Article : Google Scholar
59	Gallois A and Bhardwaj N: Dendritic cell-targeted approaches to modulate immune dysfunction in the tumor microenvironment. Front Immunol. 4(436)2013.PubMed/NCBI View Article : Google Scholar
60	Campbell KS and Hasegawa J: Natural killer cell biology: An update and future directions. J Allergy Clin Immunol. 132:536–544. 2013.PubMed/NCBI View Article : Google Scholar
61	Caligiuri MA: Human natural killer cells. Blood. 112:461–469. 2008.PubMed/NCBI View Article : Google Scholar
62	Barrow AD, Martin CJ and Colonna M: The Natural Cytotoxicity Receptors in Health and Disease. Front Immunol. 10(909)2019.PubMed/NCBI View Article : Google Scholar
63	Goding SR, Yu S, Bailey LM, Lotze MT and Basse PH: Adoptive transfer of natural killer cells promotes the anti-tumor efficacy of T cells. Clin Immunol. 177:76–86. 2017.PubMed/NCBI View Article : Google Scholar
64	Overacre-Delgoffe AE, Chikina M, Dadey RE, Yano H, Brunazzi EA, Shayan G, Horne W, Moskovitz JM, Kolls JK, Sander C, et al: Interferon-γ Drives T_reg fragility to promote anti-tumor immunity. Cell. 169:1130–1141.e11. 2017.PubMed/NCBI View Article : Google Scholar
65	Nikzad R, Angelo LS, Aviles-Padilla K, Le DT, Singh VK, Bimler L, Vukmanovic-Stejic M, Vendrame E, Ranganath T, Simpson L, et al: Human natural killer cells mediate adaptive immunity to viral antigens. Sci Immunol. 4(eaat8116)2019.PubMed/NCBI View Article : Google Scholar
66	Tong L, Jiménez-Cortegana C, Tay AHM, Wickström S, Galluzzi L and Lundqvist A: NK cells and solid tumors: Therapeutic potential and persisting obstacles. Mol Cancer. 21(206)2022.PubMed/NCBI View Article : Google Scholar
67	Habif G, Crinier A, André P, Vivier E and Narni-Mancinelli E: Targeting natural killer cells in solid tumors. Cell Mol Immunol. 16:415–422. 2019.PubMed/NCBI View Article : Google Scholar
68	Hoechst B, Voigtlaender T, Ormandy L, Gamrekelashvili J, Zhao F, Wedemeyer H, Lehner F, Manns MP, Greten TF and Korangy F: Myeloid derived suppressor cells inhibit natural killer cells in patients with hepatocellular carcinoma via the NKp30 receptor. Hepatology. 50:799–807. 2009.PubMed/NCBI View Article : Google Scholar
69	Hasmim M, Messai Y, Ziani L, Thiery J, Bouhris JH, Noman MZ and Chouaib S: Critical role of tumor microenvironment in shaping NK cell functions: Implication of hypoxic stress. Front Immunol. 6(482)2015.PubMed/NCBI View Article : Google Scholar
70	Castriconi R, Cantoni C, Della Chiesa M, Vitale M, Marcenaro E, Conte R, Biassoni R, Bottino C, Moretta L and Moretta A: Transforming growth factor beta 1 inhibits expression of NKp30 and NKG2D receptors: Consequences for the NK-mediated killing of dendritic cells. Proc Natl Acad Sci USA. 100:4120–4125. 2003.PubMed/NCBI View Article : Google Scholar
71	Balsamo M, Scordamaglia F, Pietra G, Manzini C, Cantoni C, Boitano M, Queirolo P, Vermi W, Facchetti F, Moretta A, et al: Melanoma-associated fibroblasts modulate NK cell phenotype and antitumor cytotoxicity. Proc Natl Acad Sci USA. 106:20847–20852. 2009.PubMed/NCBI View Article : Google Scholar
72	Li T, Yang Y, Hua X, Wang G, Liu W, Jia C, Tai Y, Zhang Q and Chen G: Hepatocellular carcinoma-associated fibroblasts trigger NK cell dysfunction via PGE2 and IDO. Cancer Lett. 318:154–161. 2012.PubMed/NCBI View Article : Google Scholar
73	Jourdan P, Abbal C, Noraz N, Hori T, Uchiyama T, Vendrell JP, Bousquet J, Taylor N, Pène J and Yssel H: IL-4 induces functional cell-surface expression of CXCR4 on human T cells. J Immunol. 160:4153–4157. 1998.PubMed/NCBI
74	Sallusto F, Mackay CR and Lanzavecchia A: Selective expression of the eotaxin receptor CCR3 by human T helper 2 cells. Science. 277:2005–2007. 1997.PubMed/NCBI View Article : Google Scholar
75	Zingoni A, Soto H, Hedrick JA, Stoppacciaro A, Storlazzi CT, Sinigaglia F, D'Ambrosio D, O'Garra A, Robinson D, Rocchi M, et al: The chemokine receptor CCR8 is preferentially expressed in Th2 but not Th1 cells. J Immunol. 161:547–551. 1998.PubMed/NCBI
76	Nagata K, Tanaka K, Ogawa K, Kemmotsu K, Imai T, Yoshie O, Abe H, Tada K, Nakamura M, Sugamura K and Takano S: Selective expression of a novel surface molecule by human Th2 cells in vivo. J Immunol. 162:1278–1286. 1999.PubMed/NCBI
77	Lauerova L, Dusek L, Simickova M, Kocák I, Vagundová M, Zaloudík J and Kovarík J: Malignant melanoma associates with Th1/Th2 imbalance that coincides with disease progression and immunotherapy response. Neoplasma. 49:159–166. 2002.PubMed/NCBI
78	Savetsky IL, Ghanta S, Gardenier JC, Torrisi JS, García Nores GD, Hespe GE, Nitti MD, Kataru RP and Mehrara BJ: Th2 cytokines inhibit lymphangiogenesis. PLoS One. 10(e0126908)2015.PubMed/NCBI View Article : Google Scholar
79	Nelms K, Keegan AD, Zamorano J, Ryan JJ and Paul WE: THE IL-4 RECEPTOR: Signaling mechanisms and biologic functions. Annu Rev Immunol. 17:701–738. 1999.PubMed/NCBI View Article : Google Scholar
80	Steidl C, Connors JM and Gascoyne RD: Molecular pathogenesis of Hodgkin's lymphoma: Increasing evidence of the importance of the microenvironment. J Clin Oncol. 29:1812–1826. 2011.PubMed/NCBI View Article : Google Scholar
81	Liu Z, Yang L, Cui Y, Wang X, Guo C, Huang Z, Kan Q, Liu Z and Liu Y: Il-21 enhances NK cell activation and cytolytic activity and induces Th17 cell differentiation in inflammatory bowel disease. Inflamm Bowel Dis. 15:1133–1144. 2009.PubMed/NCBI View Article : Google Scholar
82	Fontenot JD, Gavin MA and Rudensky AY: Foxp3 programs the development and function of CD4+CD25+ regulatory T cells. Nat Immunol. 4:330–336. 2003.PubMed/NCBI View Article : Google Scholar
83	Hori S, Nomura T and Sakaguchi S: Control of Regulatory T cell development by the transcription factor Foxp3. Science. 299:1057–1061. 2003.PubMed/NCBI View Article : Google Scholar
84	Kondrack RM, Harbertson J, Tan JT, McBreen ME, Surh CD and Bradley LM: Interleukin 7 regulates the survival and generation of memory CD4 cells. J Exp Med. 198:1797–1806. 2003.PubMed/NCBI View Article : Google Scholar
85	Dilek N, Poirier N, Hulin P, Coulon F, Mary C, Ville S, Vie H, Clémenceau B, Blancho G and Vanhove B: Targeting CD28, CTLA-4 and PD-L1 Costimulation Differentially Controls Immune Synapses and Function of Human Regulatory and Conventional T-Cells. PLoS One. 8(e83139)2013.PubMed/NCBI View Article : Google Scholar
86	Cohen AD, Schaer DA, Liu C, Li Y, Hirschhorn-Cymmerman D, Kim SC, Diab A, Rizzuto G, Duan F, Perales MA, et al: Agonist Anti-GITR monoclonal antibody induces melanoma tumor immunity in mice by altering regulatory T cell stability and intra-tumor accumulation. PLoS One. 5(e10436)2010.PubMed/NCBI View Article : Google Scholar
87	Hemon P, Jean-Louis F, Ramgolam K, Brignone C, Viguier M, Bachelez H, Triebel F, Charron D, Aoudjit F, Al-Daccak R and Michel L: MHC class II engagement by its ligand LAG-3 (CD223) contributes to melanoma resistance to apoptosis. J Immunol. 186:5173–5183. 2011.PubMed/NCBI View Article : Google Scholar
88	Paluskievicz CM, Cao X, Abdi R, Zheng P, Liu Y and Bromberg JS: T regulatory cells and priming the suppressive tumor microenvironment. Front Immunol. 10(2453)2019.PubMed/NCBI View Article : Google Scholar
89	Shan F, Somasundaram A, Bruno TC, Workman CJ and Vignali DAA: Therapeutic targeting of regulatory T cells in cancer. Trends Cancer. 8:944–961. 2022.PubMed/NCBI View Article : Google Scholar
90	Curran MA, Montalvo W, Yagita H and Allison JP: PD-1 and CTLA-4 combination blockade expands infiltrating T cells and reduces regulatory T and myeloid cells within B16 melanoma tumors. Proc Natl Acad Sci USA. 107:4275–4280. 2010.PubMed/NCBI View Article : Google Scholar
91	Goldberg MV and Drake CG: LAG-3 in cancer immunotherapy. Curr Top Microbiol Immunol. 344:269–278. 2011.PubMed/NCBI View Article : Google Scholar
92	Cullen SP, Brunet M and Martin SJ: Granzymes in cancer and immunity. Cell Death Differ. 17:616–623. 2010.PubMed/NCBI View Article : Google Scholar
93	Mittal SK, Cho KJ, Ishido S and Roche PA: Interleukin 10 (IL-10)-mediated Immunosuppression: MARCH-I induction regulates antigen presentation by macrophages but not dendritic cells. J Biol Chem. 290:27158–27167. 2015.PubMed/NCBI View Article : Google Scholar
94	Wrzesinski SH, Wan YY and Flavell RA: Transforming growth factor-beta and the immune response: Implications for anticancer therapy. Clin Cancer Res. 13:5262–5270. 2007.PubMed/NCBI View Article : Google Scholar
95	Pylayeva-Gupta Y: Molecular pathways: Interleukin-35 in autoimmunity and cancer. Clin Cancer Res. 22:4973–4978. 2016.PubMed/NCBI View Article : Google Scholar
96	Lim HW, Hillsamer P, Banham AH and Kim CH: Cutting edge: Direct suppression of B cells by CD4+ CD25+ regulatory T cells. J Immunol. 175:4180–4183. 2005.PubMed/NCBI View Article : Google Scholar
97	Huang B, Pan PY, Li Q, Sato AI, Levy DE, Bromberg J, Divino CM and Chen SH: Gr-1+CD115+ immature myeloid suppressor cells mediate the development of tumor-induced T regulatory cells and T-cell anergy in tumor-bearing host. Cancer Res. 66:1123–1131. 2006.PubMed/NCBI View Article : Google Scholar
98	Vasconcelos DP, Costa M, Amaral IF, Barbosa MA, Águas AP and Barbosa JN: Modulation of the inflammatory response to chitosan through M2 macrophage polarization using pro-resolution mediators. Biomaterials. 37:116–123. 2015.PubMed/NCBI View Article : Google Scholar
99	Porta C, Riboldi E, Ippolito A and Sica A: Molecular and epigenetic basis of macrophage polarized activation. Semin Immunol. 27:237–248. 2015.PubMed/NCBI View Article : Google Scholar
100	Che F, Heng X, Zhang H, Su Q, Zhang B, Chen Y, Zhang Z, Du Y and Wang L: Novel B7-H4-mediated crosstalk between human non-Hodgkin lymphoma cells and tumor-associated macrophages leads to immune evasion via secretion of IL-6 and IL-10. Cancer Immunol Immunother. 66:717–729. 2017.PubMed/NCBI View Article : Google Scholar
101	Wang Q, Tang Y, Yu H, Yin Q, Li M, Shi L, Zhang W, Li D and Li L: CCL18 from tumor-cells promotes epithelial ovarian cancer metastasis via mTOR signaling pathway. Mol Carcinog. 55:1688–1699. 2016.PubMed/NCBI View Article : Google Scholar
102	Goswami KK, Ghosh T, Ghosh S, Sarkar M, Bose A and Baral R: Tumor promoting role of anti-tumor macrophages in tumor microenvironment. Cell Immunol. 316:1–10. 2017.PubMed/NCBI View Article : Google Scholar
103	Hesse M, Modolell M, La Flamme AC, Schito M, Fuentes JM, Cheever AW, Pearce EJ and Wynn TA: Differential regulation of nitric oxide synthase-2 and arginase-1 by type 1/type 2 cytokines in vivo: Granulomatous pathology is shaped by the pattern of L-arginine metabolism. J Immunol. 167:6533–6544. 2001.PubMed/NCBI View Article : Google Scholar
104	Rodriguez PC, Quiceno DG, Zabaleta J, Ortiz B, Zea AH, Piazuelo MB, Delgado A, Correa P, Brayer J, Sotomayor EM, et al: Arginase I production in the tumor microenvironment by mature myeloid cells inhibits T-cell receptor expression and antigen-specific T-cell responses. Cancer Res. 64:5839–5849. 2004.PubMed/NCBI View Article : Google Scholar
105	Dallavalasa S, Beeraka NM, Basavaraju CG, Tulimilli SV, Sadhu SP, Rajesh K, Aliev G and Madhunapantula SV: The role of tumor associated macrophages (TAMs) in cancer progression, chemoresistance, angiogenesis and metastasis-current status. Curr Med Chem. 28:8203–8236. 2021.PubMed/NCBI View Article : Google Scholar
106	Pan Y, Yu Y, Wang X and Zhang T: Tumor-Associated macrophages in tumor immunity. Front Immunol. 11(583084)2020.PubMed/NCBI View Article : Google Scholar
107	Liu C, Chikina M, Deshpande R, Menk AV, Wang T, Tabib T, Brunazzi EA, Vignali KM, Sun M, Stolz DB, et al: Treg cells promote the SREBP1-Dependent metabolic fitness of tumor-promoting macrophages via repression of CD8 + T cell-derived interferon-γ. Immunity. 51:381–397.e6. 2019.PubMed/NCBI View Article : Google Scholar
108	Kumar V, Cheng P, Condamine T, Mony S, Languino LR, McCaffrey JC, Hockstein N, Guarino M, Masters G, Penman E, et al: CD45 phosphatase inhibits STAT3 transcription factor activity in myeloid cells and promotes tumor-associated macrophage differentiation. Immunity. 44:303–315. 2016.PubMed/NCBI View Article : Google Scholar
109	Marvel D and Gabrilovich DI: Myeloid-derived suppressor cells in the tumor microenvironment: Expect the unexpected. J Clin Invest. 125:3356–3364. 2015.PubMed/NCBI View Article : Google Scholar
110	Greten TF, Manns MP and Korangy F: Myeloid derived suppressor cells in human diseases. Int Immunopharmacol. 11:802–807. 2011.PubMed/NCBI View Article : Google Scholar
111	Filipazzi P, Huber V and Rivoltini L: Phenotype, function and clinical implications of myeloid-derived suppressor cells in cancer patients. Cancer Immunol Immunother. 61:255–263. 2012.PubMed/NCBI View Article : Google Scholar
112	Li H, Han Y, Guo Q, Zhang M and Cao X: Cancer-expanded myeloid-derived suppressor cells induce anergy of NK cells through membrane-bound TGF-beta 1. J Immunol. 182:240–249. 2009.PubMed/NCBI View Article : Google Scholar
113	Liu C, Yu S, Kappes J, Wang J, Grizzle WE, Zinn KR and Zhang HG: Expansion of spleen myeloid suppressor cells represses NK cell cytotoxicity in tumor-bearing host. Blood. 109:4336–4342. 2007.PubMed/NCBI View Article : Google Scholar
114	Sinha P, Clements VK, Bunt SK, Albelda SM and Ostrand-Rosenberg S: Cross-talk between myeloid-derived suppressor cells and macrophages subverts tumor immunity toward a type 2 response. J Immunol. 179:977–983. 2007.PubMed/NCBI View Article : Google Scholar
115	Rodriguez PC, Quiceno DG and Ochoa AC: l-arginine availability regulates T-lymphocyte cell-cycle progression. Blood. 109:1568–1573. 2007.PubMed/NCBI View Article : Google Scholar
116	Srivastava MK, Sinha P, Clements VK, Rodriguez P and Ostrand-Rosenberg S: Myeloid-derived suppressor cells inhibit T-cell activation by depleting cystine and cysteine. Cancer Res. 70:68–77. 2010.PubMed/NCBI View Article : Google Scholar
117	Harari O and Liao JK: Inhibition of MHC II gene transcription by nitric oxide and antioxidants. Curr Pharm Des. 10:893–898. 2004.PubMed/NCBI View Article : Google Scholar
118	Dugast AS, Haudebourg T, Coulon F, Heslan M, Haspot F, Poirier N, Vuillefroy de Silly R, Usal C, Smit H, Martinet B, et al: Myeloid-derived suppressor cells accumulate in kidney allograft tolerance and specifically suppress effector T cell expansion. J Immunol. 180:7898–7906. 2008.PubMed/NCBI View Article : Google Scholar
119	Kusmartsev S, Nefedova Y, Yoder D and Gabrilovich DI: Antigen-specific inhibition of CD8+ T cell response by immature myeloid cells in cancer is mediated by reactive oxygen species. J Immunol. 172:989–999. 2004.PubMed/NCBI View Article : Google Scholar
120	Nagaraj S, Gupta K, Pisarev V, Kinarsky L, Sherman S, Kang L, Herber DL, Schneck J and Gabrilovich DI: Altered recognition of antigen is a mechanism of CD8+ T cell tolerance in cancer. Nat Med. 13:828–835. 2007.PubMed/NCBI View Article : Google Scholar
121	Hanson EM, Clements VK, Sinha P, Ilkovitch D and Ostrand-Rosenberg S: Myeloid-derived suppressor cells down-regulate L-selectin expression on CD4+ and CD8+ T cells. J Immunol. 183:937–944. 2009.PubMed/NCBI View Article : Google Scholar
122	Saleem SJ, Martin RK, Morales JK, Sturgill JL, Gibb DR, Graham L, Bear HD, Manjili MH, Ryan JJ and Conrad DH: Cutting edge: Mast cells critically augment myeloid-derived suppressor cell activity. J Immunol. 189:511–515. 2012.PubMed/NCBI View Article : Google Scholar
123	Oshi M, Asaoka M, Tokumaru Y, Yan L, Matsuyama R, Ishikawa T, Endo I and Takabe K: CD8 T cell score as a prognostic biomarker for triple negative breast cancer. Int J Mol Sci. 21(6968)2020.PubMed/NCBI View Article : Google Scholar
124	Peiper M, Goedegebuure PS, Linehan DC, Ganguly E, Douville CC and Eberlein TJ: The HER2/neu-derived peptide p654-662 is a tumor-associated antigen in human pancreatic cancer recognized by cytotoxic T lymphocytes. Eur J Immunol. 27:1115–1123. 1997.PubMed/NCBI View Article : Google Scholar
125	Cui TX, Kryczek I, Zhao L, Zhao E, Kuick R, Roh MH, Vatan L, Szeliga W, Mao Y, Thomas DG, et al: Myeloid-derived suppressor cells enhance stemness of cancer cells by inducing microRNA101 and suppressing the corepressor CtBP2. Immunity. 39:611–621. 2013.PubMed/NCBI View Article : Google Scholar
126	Horikawa N, Abiko K, Matsumura N, Hamanishi J, Baba T, Yamaguchi K, Yoshioka Y, Koshiyama M and Konishi I: Expression of Vascular Endothelial Growth Factor in Ovarian Cancer Inhibits Tumor Immunity through the Accumulation ofMyeloid-Derived Suppressor Cells. Clinical Cancer Research. 23:2017.PubMed/NCBI View Article : Google Scholar
127	Vanderstraeten A, Luyten C, Verbist G, Tuyaerts S and Amant F: Mapping the immunosuppressive environment in uterine tumors: Implications for immunotherapy. Cancer Immunol Immunother. 63:545–557. 2014.PubMed/NCBI View Article : Google Scholar
128	Kawano M, Mabuchi S, Matsumoto Y, Sasano T, Takahashi R, Kuroda H, Kozasa K, Hashimoto K, Isobe A, Sawada K, et al: The significance of G-CSF expression and myeloid-derived suppressor cells in the chemoresistance of uterine cervical cancer. Sci Rep. 5(18217)2015.PubMed/NCBI View Article : Google Scholar
129	Kusuda T, Shigemasa K, Arihiro K, Fujii T, Nagai N and Ohama K: Relative expression levels of Th1 and Th2 cytokine mRNA are independent prognostic factors in patients with ovarian cancer. Oncol Rep. 13:1153–1158. 2005.PubMed/NCBI
130	Tsukui T, Hildesheim A, Schiffman MH, Lucci J III, Contois D, Lawler P, Rush BB, Lorincz AT, Corrigan A, Burk RD, et al: Interleukin 2 production in vitro by peripheral lymphocytes in response to human papillomavirus-derived peptides: Correlation with cervical pathology. Cancer Res. 56:3967–3974. 1996.PubMed/NCBI
131	Chang WC, Li CH, Huang SC, Chang DY, Chou LY and Sheu BC: Clinical significance of regulatory T cells and CD8+ effector populations in patients with human endometrial carcinoma. Cancer. 116:5777–5788. 2010.PubMed/NCBI View Article : Google Scholar
132	Dutsch-Wicherek MM, Szubert S, Dziobek K, Wisniewski M, Lukaszewska E, Wicherek L, Jozwicki W, Rokita W and Koper K: Analysis of the treg cell population in the peripheral blood of ovarian cancer patients in relation to the long-term outcomes. Ginekol Pol. 90:179–184. 2019.PubMed/NCBI View Article : Google Scholar
133	Hou F, Li Z, Ma D, Zhang W, Zhang Y, Zhang T, Kong B and Cui B: Distribution of Th17 cells and Foxp3-expressing T cells in tumor-infiltrating lymphocytes in patients with uterine cervical cancer. Clin Chim Acta. 413:1848–1854. 2012.PubMed/NCBI View Article : Google Scholar
134	Visser J, Nijman HW, Hoogenboom BN, Jager P, van Baarle D, Schuuring E, Abdulahad W, Miedema F, van der Zee AG and Daemen T: Frequencies and role of regulatory T cells in patients with (pre)malignant cervical neoplasia. Clin Exp Immunol. 150:199–209. 2007.PubMed/NCBI View Article : Google Scholar
135	Mustea A, Braicu EI, Koensgen D, Yuan S, Sun PM, Stamatian F, Lichtenegger W, Chen FC, Chekerov R and Sehouli J: Monitoring of IL-10 in the serum of patients with advanced ovarian cancer: Results from a prospective pilot-study. Cytokine. 45:8–11. 2009.PubMed/NCBI View Article : Google Scholar
136	Zhang M, He Y, Sun X, Li Q, Wang W, Zhao A and Di W: A high M1/M2 ratio of tumor-associated macrophages is associated with extended survival in ovarian cancer patients. J Ovarian Res. 7(19)2014.PubMed/NCBI View Article : Google Scholar
137	Lan C, Huang X, Lin S, Huang H, Cai Q, Wan T, Lu J and Liu J: Expression of M2-polarized macrophages is associated with poor prognosis for advanced epithelial ovarian cancer. Technol Cancer Res Treat. 12:259–267. 2013.PubMed/NCBI View Article : Google Scholar
138	Hashimoto I, Kodama J, Seki N, Hongo A, Miyagi Y, Yoshinouchi M and Kudo T: Macrophage infiltration and angiogenesis in endometrial cancer. Anticancer Res. 20 (6C):853–856. 2000.PubMed/NCBI
139	Ding H, Cai J, Mao M, Fang Y, Huang Z, Jia J, Li T, Xu L, Wang J, Zhou J, et al: Tumor-associated macrophages induce lymphangiogenesis in cervical cancer via interaction with tumor cells. APMIS. 122:1059–1069. 2014.PubMed/NCBI View Article : Google Scholar
140	Chen XJ, Han LF, Wu XG, Wei WF, Wu LF, Yi HY, Yan RM, Bai XY, Zhong M, Yu YH, et al: Clinical Significance of CD163+ and CD68+ tumor-associated macrophages in high-risk HPV-related cervical cancer. J Cancer. 8:3868–3875. 2017.PubMed/NCBI View Article : Google Scholar
141	Lai P, Rabinowich H, Crowley-Nowick PA, Bell MC, Mantovani G and Whiteside TL: Alterations in expression and function of signal transducing proteins in tumor-associated T and natural killer cells in ovarian carcinoma. Biochem Soc Trans. 25(218S)1997.PubMed/NCBI View Article : Google Scholar
142	Gras Navarro A, Björklund AT and Chekenya M: Therapeutic potential and challenges of natural killer cells in treatment of solid tumors. Front Immunol. 6(202)2015.PubMed/NCBI View Article : Google Scholar
143	Wu Y, Ye S, Goswami S, Pei X, Xiang L, Zhang X and Yang H: Clinical significance of peripheral blood and tumor tissue lymphocyte subsets in cervical cancer patients. BMC Cancer. 20(173)2020.PubMed/NCBI View Article : Google Scholar
144	Iva T, Lenka K, Michal H, Petr S, Jan L, Ladislav P, et al: Mature dendritic cells correlate with favorable immune infiltrate and improved prognosis in ovarian carcinoma patients. Journal for Immunotherapy of Cancer. 6:2018.PubMed/NCBI View Article : Google Scholar
145	Lijun Z, Xin Z, Danhua S, Xiaoping L, Jianliu W, Huilan W and Lihui W: Tumor-Infiltrating Dendritic Cells May Be Used as Clinicopathologic Prognostic Factors in Endometrial Carcinoma. Int J Gynecol Cancer. 22:836–841. 2012.PubMed/NCBI View Article : Google Scholar
146	Mendoza L, Bubeník J, Símová J, Korb J, Bieblová J, Vonka V, Indrová M, Mikysková R and Jandlová T: Tumour-inhibitory effects of dendritic cells administered at the site of HPV 16-induced neoplasms. Folia Biol (Praha). 48:114–119. 2002.PubMed/NCBI
147	Sato E, Olson SH, Ahn J, Bundy B, Nishikawa H, Qian F, Jungbluth AA, Frosina D, Gnjatic S, Ambrosone C, et al: Intraepithelial CD8+ tumor-infiltrating lymphocytes and a high CD8+/regulatory T cell ratio are associated with favorable prognosis in ovarian cancer. Proc Natl Acad Sci USA. 102:18538–18543. 2005.PubMed/NCBI View Article : Google Scholar
148	Kondratiev S, Sabo E, Yakirevich E, Lavie O and Resnick MB: Intratumoral CD8+ T lymphocytes as a prognostic factor of survival in endometrial carcinoma. Clin Cancer Res. 10:4450–4456. 2004.PubMed/NCBI View Article : Google Scholar
149	Ordoñez R, Henríquez-Hernández LA, Federico M, Valenciano A, Pinar B, Lloret M, Bordón E, Rodríguez-Gallego C and Lara PC: Radio-induced apoptosis of peripheral blood CD8 T lymphocytes is a novel prognostic factor for survival in cervical carcinoma patients. Strahlenther Onkol. 190:210–216. 2014.PubMed/NCBI View Article : Google Scholar
150	Miyasaka Y, Yoshimoto Y, Murata K, Noda SE, Ando K, Ebara T, Okonogi N, Kaminuma T, Yamada S, Ikota H, et al: Treatment outcomes of patients with adenocarcinoma of the uterine cervix after definitive radiotherapy and the prognostic impact of tumor-infiltrating CD8+ lymphocytes in pre-treatment biopsy specimens: A multi-institutional retrospective study. J Radiat Res. 61:275–284. 2020.PubMed/NCBI View Article : Google Scholar
151	Spiess PJ, Yang JC and Rosenberg SA: In vivo antitumor activity of tumor-infiltrating lymphocytes expanded in recombinant interleukin-2. J Natl Cancer Inst. 79:1067–1075. 1987.PubMed/NCBI
152	Krishna S, Lowery FJ, Copeland AR, Bahadiroglu E, Mukherjee R, Jia L, Anibal JT, Sachs A, Adebola SO, Gurusamy D, et al: Stem-like CD8 T cells mediate response of adoptive cell immunotherapy against human cancer. Science. 370:1328–1334. 2020.PubMed/NCBI View Article : Google Scholar
153	J SP, C YJ and RS: In vivo antitumor activity of tumor-infiltrating lymphocytes expanded in recombinant interleukin-2. Journal of the National Cancer Institute. 79:1987.PubMed/NCBI
154	Kumar A, Watkins R and Vilgelm AE: Cell therapy with TILs: Training and taming T cells to fight cancer. Front Immunol. 12(690499)2021.PubMed/NCBI View Article : Google Scholar
155	Rohaan MW, Wilgenhof S and Haanen JBAG: Adoptive cellular therapies: The current landscape. Virchows Arch. 474:449–461. 2018.PubMed/NCBI View Article : Google Scholar
156	Gudiol C, Lewis RE, Strati P and Kontoyiannis DP: Chimeric antigen receptor T-cell therapy for the treatment of lymphoid malignancies: Is there an excess risk for infection? Lancet Haematol. 8:e216–e228. 2021.PubMed/NCBI View Article : Google Scholar
157	Rosenberg SA, Yang JC, Sherry RM, Kammula US, Hughes MS, Phan GQ, Citrin DE, Restifo NP, Robbins PF, Wunderlich JR, et al: Durable complete responses in heavily pretreated patients with metastatic melanoma using T-cell transfer immunotherapy. Clin Cancer Res. 17:4550–4457. 2011.PubMed/NCBI View Article : Google Scholar
158	Andersen R, Donia M, Ellebaek E, Borch TH, Kongsted P, Iversen TZ, Hölmich LR, Hendel HW, Met Ö, Andersen MH, et al: Long-Lasting complete responses in patients with metastatic melanoma after adoptive cell therapy with tumor-infiltrating lymphocytes and an attenuated IL2 regimen. Clin Cancer Res. 22:3734–3745. 2016.PubMed/NCBI View Article : Google Scholar
159	Stevanović S, Draper LM, Langhan MM, Campbell TE, Kwong ML, Wunderlich JR, Dudley ME, Yang JC, Sherry RM, Kammula US, et al: Complete regression of metastatic cervical cancer after treatment with human papillomavirus-targeted tumor-infiltrating T cells. J Clin Oncol. 33:1543–1550. 2015.PubMed/NCBI View Article : Google Scholar
160	Donnem T, Hald SM, Paulsen E, Richardsen E, Al-Saad S, Kilvaer TK, Brustugun OT, Helland A, Lund-Iversen M, Poehl M, et al: Stromal CD8+ T-cell Density-A promising supplement to TNM staging in non-small cell lung cancer. Clin Cancer Res. 21:2635–2643. 2015.PubMed/NCBI View Article : Google Scholar
161	James FR, Jiminez-Linan M, Alsop J, Mack M, Song H, Brenton JD, Pharoah PDP and Ali HR: Association between tumour infiltrating lymphocytes, histotype and clinical outcome in epithelial ovarian cancer. BMC Cancer. 17(657)2017.PubMed/NCBI View Article : Google Scholar
162	Stanton SE and Disis ML: Clinical significance of tumor-infiltrating lymphocytes in breast cancer. J Immunother Cancer. 4(59)2016.PubMed/NCBI View Article : Google Scholar
163	Sideras K, Biermann K, Yap K, Mancham S, Boor PPC, Hansen BE, Stoop HJA, Peppelenbosch MP, van Eijck CH, Sleijfer S, et al: Tumor cell expression of immune inhibitory molecules and tumor-infiltrating lymphocyte count predict cancer-specific survival in pancreatic and ampullary cancer. Int J Cancer. 141:572–582. 2017.PubMed/NCBI View Article : Google Scholar
164	Clemente O, Ottaiano A, Di Lorenzo G, Bracigliano A, Lamia S, Cannella L, Pizzolorusso A, Di Marzo M, Santorsola M, De Chiara A, et al: Is immunotherapy in the future of therapeutic management of sarcomas? J Transl Med. 19(173)2021.PubMed/NCBI View Article : Google Scholar
165	Radvanyi LG: Tumor-Infiltrating lymphocyte therapy: Addressing prevailing questions. Cancer J. 21:450–464. 2015.PubMed/NCBI View Article : Google Scholar
166	Aoki Y, Takakuwa K, Kodama S, Tanaka K, Takahashi M, Tokunaga A and Takahashi T: Use of adoptive transfer of tumor-infiltrating lymphocytes alone or in combination with cisplatin-containing chemotherapy in patients with epithelial ovarian cancer. Cancer Res. 51:1934–1939. 1991.PubMed/NCBI
167	Fujita K, Ikarashi H, Takakuwa K, Kodama S, Tokunaga A, Takahashi T and Tanaka K: Prolonged disease-free period in patients with advanced epithelial ovarian cancer after adoptive transfer of tumor-infiltrating lymphocytes. Clin Cancer Res. 1:501–507. 1995.PubMed/NCBI
168	Santoiemma PP and Powell DJ Jr: Tumor infiltrating lymphocytes in ovarian cancer. Cancer Biol Ther. 16:807–820. 2015.PubMed/NCBI View Article : Google Scholar
169	Jazaeri AA, Zsiros E, Amaria RN, Artz AS, Edwards RP, Wenham RM, Slomovitz BM, Walther A, Thomas SS, Chesney JA, et al: Safety and efficacy of adoptive cell transfer using autologous tumor infiltrating lymphocytes (LN-145) for treatment of recurrent, metastatic, or persistent cervical carcinoma. J Clin Oncol. 37 (15_suppl)(S2538)2019.
170	KF HI, KT SK, AT TT, et al: Prolonged disease-free period in patients with advanced epithelial ovarian cancer after adoptive transfer of tumor-infiltrating lymphocytes. J Clinical Cancer Research: An Official Journal of the American Association for Cancer Research 1, 1995.
171	Seliktar-Ofir S, Merhavi-Shoham E, Itzhaki O, Yunger S, Markel G, Schachter J and Besser MJ: Selection of shared and neoantigen-reactive T cells for adoptive cell therapy based on CD137 separation. Front Immunol. 8(1211)2017.PubMed/NCBI View Article : Google Scholar
172	Inozume T, Hanada K, Wang QJ, Ahmadzadeh M, Wunderlich JR, Rosenberg SA and Yang JC: Selection of CD8+PD-1+ lymphocytes in fresh human melanomas enriches for tumor-reactive T cells. J Immunother. 33:956–964. 2010.PubMed/NCBI View Article : Google Scholar
173	Manson G, Norwood J, Marabelle A, Kohrt H and Houot R: Biomarkers associated with checkpoint inhibitors. Ann Oncol. 27:1199–1206. 2016.PubMed/NCBI View Article : Google Scholar
174	Wolf B, Zimmermann S, Arber C, Irving M, Trueb L and Coukos G: Safety and tolerability of adoptive cell therapy in cancer. Drug Saf. 42:315–334. 2019.PubMed/NCBI View Article : Google Scholar
175	Burger SR: Current regulatory issues in cell and tissue therapy. Cytotherapy. 5:289–298. 2003.PubMed/NCBI View Article : Google Scholar
176	Cruz CR, Hanley PJ, Liu H, Torrano V, Lin YF, Arce JA, Gottschalk S, Savoldo B, Dotti G, Louis CU, et al: Adverse events following infusion of T cells for adoptive immunotherapy: A 10-year experience. Cytotherapy. 12:743–749. 2010.PubMed/NCBI View Article : Google Scholar
177	Dudley ME, Wunderlich JR, Robbins PF, Yang JC, Hwu P, Schwartzentruber DJ, Topalian SL, Sherry R, Restifo NP, Hubicki AM, et al: Cancer regression and autoimmunity in patients after clonal repopulation with antitumor lymphocytes. Science. 298:850–854. 2002.PubMed/NCBI View Article : Google Scholar
178	Shimabukuro-Vornhagen A, Gödel P, Subklewe M, Stemmler HJ, Schlößer HA, Schlaak M, Kochanek M, Böll B and von Bergwelt-Baildon MS: Cytokine release syndrome. J Immunother Cancer. 6(56)2018.PubMed/NCBI View Article : Google Scholar
179	Liu D and Zhao J: Cytokine release syndrome: Grading, modeling, and new therapy. J Hematol Oncol. 11(121)2018.PubMed/NCBI View Article : Google Scholar
180	Xiao BF, Zhang JT, Zhu YG, Cui XR, Lu ZM, Yu BT and Wu N: Chimeric antigen receptor T-Cell therapy in lung cancer: Potential and challenges. Front Immunol. 12(782775)2021.PubMed/NCBI View Article : Google Scholar
181	Stevanović S, Pasetto A, Helman SR, Gartner JJ, Prickett TD, Howie B, Robins HS, Robbins PF, Klebanoff CA, Rosenberg SA and Hinrichs CS: Landscape of immunogenic tumor antigens in successful immunotherapy of virally induced epithelial cancer. Science. 356:200–205. 2017.PubMed/NCBI View Article : Google Scholar
182	Disis ML, Dang Y, Coveler AL, Marzbani E, Kou ZC, Childs JS, Fintak P, Higgins DM, Reichow J, Waisman J and Salazar LG: HER-2/neu vaccine-primed autologous T-cell infusions for the treatment of advanced stage HER-2/neu expressing cancers. Cancer Immunol Immunother. 63:101–109. 2014.PubMed/NCBI View Article : Google Scholar
183	Kyi C, Doubrovina E, Zhou Q, Kravetz S, Iasonos A, Aghajanian C, Sabbatini P, Spriggs D, O'Reilly RJ and O'Cearbhaill RE: Phase I dose escalation safety and feasibility study of autologous WT1-sensitized T cells for the treatment of patients with recurrent ovarian cancer. J Immunother Cancer. 9(e002752)2021.PubMed/NCBI View Article : Google Scholar
184	Zacharakis N, Huq LM, Seitter SJ, Kim SP, Gartner JJ, Sindiri S, Hill VK, Li YF, Paria BC, Ray S, et al: Breast cancers are immunogenic: Immunologic analyses and a phase II pilot clinical trial using mutation-reactive autologous lymphocytes. J Clin Oncol. 40:1741–1754. 2022.PubMed/NCBI View Article : Google Scholar
185	Westergaard MCW, Andersen R, Chong C, Kjeldsen JW, Pedersen M, Friese C, Hasselager T, Lajer H, Coukos G, Bassani-Sternberg M, et al: Tumour-reactive T cell subsets in the microenvironment of ovarian cancer. Br J Cancer. 120:424–434. 2019.PubMed/NCBI View Article : Google Scholar
186	Tsimberidou AM, Guenther K, Andersson BS, Mendrzyk R, Alpert A, Wagner C, Nowak A, Aslan K, Satelli A, Richter F, et al: Feasibility and safety of personalized, multi-target, adoptive cell therapy (IMA101): First-In-Human clinical trial in patients with advanced metastatic cancer. Cancer Immunol Res. 11:925–945. 2023.PubMed/NCBI View Article : Google Scholar
187	Stevanović S, Helman SR, Wunderlich JR, Langhan MM, Doran SL, Kwong MLM, Somerville RPT, Klebanoff CA, Kammula US, Sherry RM, et al: A phase II study of tumor-infiltrating lymphocyte therapy for human papillomavirus-associated epithelial cancers. Clin Cancer Res. 25:1486–1493. 2019.PubMed/NCBI View Article : Google Scholar