Comprehensive analysis of signaling lymphocyte activation molecule family as a prognostic biomarker and correlation with immune infiltration in clear cell renal cell carcinoma

Song,Na; Song,Na; Song,Na; Song,Na; Wang,Ziwei; Wang,Ziwei; Wang,Ziwei; Wang,Ziwei; Shi,Pingyu; Shi,Pingyu; Shi,Pingyu; Shi,Pingyu; Cui,Kai; Cui,Kai; Cui,Kai; Cui,Kai; Fan,Yanwu; Fan,Yanwu; Fan,Yanwu; Fan,Yanwu; Zeng,Liqun; Zeng,Liqun; Zeng,Liqun; Zeng,Liqun; Di,Wenyu; Di,Wenyu; Di,Wenyu; Di,Wenyu; Li,Jinsong; Li,Jinsong; Li,Jinsong; Li,Jinsong; Su,Wei; Su,Wei; Su,Wei; Su,Wei; Wang,Haijun; Wang,Haijun; Wang,Haijun; Wang,Haijun

doi:10.3892/ol.2024.14487

Comprehensive analysis of signaling lymphocyte activation molecule family as a prognostic biomarker and correlation with immune infiltration in clear cell renal cell carcinoma

Authors:
- Na Song
- Ziwei Wang
- Pingyu Shi
- Kai Cui
- Yanwu Fan
- Liqun Zeng
- Wenyu Di
- Jinsong Li
- Wei Su
- Haijun Wang
View Affiliations

Affiliations: Department of Pathology, Xinxiang Key Laboratory of Tumor Precision Medicine, The First Affiliated Hospital of Xinxiang Medical University, Weihui, Henan 453100, P.R. China, Department of Pathology, School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang, Henan 453000, P.R. China
Published online on: June 3, 2024 https://doi.org/10.3892/ol.2024.14487
Article Number: 354
Copyright: © Song et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Clear cell renal cell carcinoma (ccRCC) is a common type of kidney cancer and accounts for 2‑3% of all cancer cases. Furthermore, a growing number of immunotherapy approaches are being used in antitumor treatment. Signaling lymphocyte activation molecule family (SLAMF) members have been well studied in several cancers, whereas their roles in ccRCC have not been investigated. The present study comprehensively assessed the molecular mechanisms of SLAMF members in ccRCC, performed using The Cancer Genome Atlas database, with analysis of gene transcription, prognosis, biological function, clinical features, tumor‑associated immune cells and the correlation with programmed cell death protein 1/programmed death‑ligand 1 immune checkpoints. Simultaneously, the Tumor Immune Dysfunction and Exclusion algorithm was used to predict the efficacy of immune checkpoint blockade (ICB) therapy in patients with high and low SLAMF expression levels. The results demonstrated that all SLAMF members were highly expressed in ccRCC, and patients with high expression levels of SLAMF1, 4, 7 and 8 had a worse prognosis that those with low expression. SLAMF members were not only highly associated with immune activation but also with immunosuppressive agents. The level of immune cell infiltration was associated with the prognosis of patients with ccRCC with high SLAMF expression. Moreover, high ICB response rates were observed in patients with high expression levels of SMALF1 and 4. In summary, SLAMF members may serve as future potential biomarkers for predicting the prognosis of ccRCC and emerge as a novel immunotherapy target.

View Figures

View References

1	Siegel RL, Miller KD, Fuchs HE and Jemal A: Cancer statistics, 2021. CA Cancer J Clin. 71:7–33. 2021. View Article : Google Scholar : PubMed/NCBI
2	Moch H, Cubilla AL, Humphrey PA, Reuter VE and Ulbright TM: The 2016 WHO classification of tumours of the urinary system and male genital organs-part A: Renal, penile, and testicular tumours. Eur Urol. 70:93–105. 2016. View Article : Google Scholar : PubMed/NCBI
3	Marchetti A, Rosellini M, Mollica V, Rizzo A, Tassinari E, Nuvola G, Cimadamore A, Santoni M, Fiorentino M, Montironi R and Massari F: The molecular characteristics of non-clear cell renal cell carcinoma: What's the story morning glory? Int J Mol Sci. 22:62372021. View Article : Google Scholar : PubMed/NCBI
4	Jiang J, Han P, Qian J, Zhang S, Wang S, Cao Q and Shao P: Knockdown of ALPK2 blocks development and progression of renal cell carcinoma. Exp Cell Res. 392:1120292020. View Article : Google Scholar : PubMed/NCBI
5	He YH, Chen C and Shi Z: The biological roles and clinical implications of microRNAs in clear cell renal cell carcinoma. J Cell Physiol. 233:4458–4465. 2018. View Article : Google Scholar : PubMed/NCBI
6	Gao S, Yan L, Zhang H, Fan X, Jiao X and Shao F: Identification of a metastasis-associated gene signature of clear cell renal cell carcinoma. Front Genet. 11:6034552021. View Article : Google Scholar : PubMed/NCBI
7	Cochetti G, Cari L, Nocentini G, Maulà V, Suvieri C, Cagnani R, Rossi De Vermandois JA and Mearini E: Detection of urinary miRNAs for diagnosis of clear cell renal cell carcinoma. Sci Rep. 10:212902020. View Article : Google Scholar : PubMed/NCBI
8	Obeng RC, Arnold RS, Ogan K, Master VA, Pattaras JG, Petros JA and Osunkoya AO: Molecular characteristics and markers of advanced clear cell renal cell carcinoma: Pitfalls due to intratumoral heterogeneity and identification of genetic alterations associated with metastasis. Int J Urol. 27:790–797. 2020. View Article : Google Scholar : PubMed/NCBI
9	Cros J, Sbidian E, Posseme K, Letierce A, Guettier C, Benoît G and Ferlicot S: Nestin expression on tumour vessels and tumour-infiltrating macrophages define a poor prognosis subgroup of pt1 clear cell renal cell carcinoma. Virchows Arch. 469:331–337. 2016. View Article : Google Scholar : PubMed/NCBI
10	Janowitz T, Welsh SJ, Zaki K, Mulders P and Eisen T: Adjuvant therapy in renal cell carcinoma-past, present, and future. Semin Oncol. 40:482–491. 2013. View Article : Google Scholar : PubMed/NCBI
11	Motzer RJ, Jonasch E, Agarwal N, Alva A, Baine M, Beckermann K, Carlo MI, Choueiri TK, Costello BA, Derweesh IH, et al: Kidney cancer, version 3.2022, NCCN clinical practice guidelines in oncology. J Natl Compr Canc Netw. 20:71–90. 2022. View Article : Google Scholar : PubMed/NCBI
12	Rosellini M, Marchetti A, Mollica V, Rizzo A, Santoni M and Massari F: Prognostic and predictive biomarkers for immunotherapy in advanced renal cell carcinoma. Nat Rev Urol. 20:133–157. 2023. View Article : Google Scholar : PubMed/NCBI
13	Wang B, Chen D and Hua H: TBC1D3 family is a prognostic biomarker and correlates with immune infiltration in kidney renal clear cell carcinoma. Mol Ther Oncolytics. 22:528–538. 2021. View Article : Google Scholar : PubMed/NCBI
14	Santoni M, Rizzo A, Mollica V, Matrana MR, Rosellini M, Faloppi L, Marchetti A, Battelli N and Massari F: The impact of gender on the efficacy of immune checkpoint inhibitors in cancer patients: The MOUSEION-01 study. Crit Rev Oncol Hematol. 170:1035962022. View Article : Google Scholar : PubMed/NCBI
15	Rizzo A, Mollica V, Dall'Olio FG, Ricci AD, Maggio I, Marchetti A, Rosellini M, Santoni M, Ardizzoni A and Massari F: Quality of life assessment in renal cell carcinoma phase II and III clinical trials published between 2010 and 2020: A systematic review. Future Oncol. 17:2671–2681. 2021. View Article : Google Scholar : PubMed/NCBI
16	Mollica V, Rizzo A, Marchetti A, Tateo V, Tassinari E, Rosellini M, Massafra R, Santoni M and Massari F: The impact of ECOG performance status on efficacy of immunotherapy and immune-based combinations in cancer patients: The MOUSEION-06 study. Clin Exp Med. 23:5039–5049. 2023. View Article : Google Scholar : PubMed/NCBI
17	Dragovich MA and Mor A: The SLAM family receptors: Potential therapeutic targets for inflammatory and autoimmune diseases. Autoimmun Rev. 17:674–682. 2018. View Article : Google Scholar : PubMed/NCBI
18	Gunes M, Rosen ST, Shachar I and Gunes EG: Signaling lymphocytic activation molecule family receptors as potential immune therapeutic targets in solid tumors. Front Immunol. 15:12974732024. View Article : Google Scholar : PubMed/NCBI
19	Farhangnia P, Ghomi SM, Mollazadehghomi S, Nickho H, Akbarpour M and Delbandi AA: SLAM-family receptors come of age as a potential molecular target in cancer immunotherapy. Front Immunol. 14:11741382023. View Article : Google Scholar : PubMed/NCBI
20	Tojjari A, Giles FJ, Vilbert M, Saeed A and Cavalcante L: SLAM modification as an immune-modulatory therapeutic approach in cancer. Cancers (Basel). 15:48082023. View Article : Google Scholar : PubMed/NCBI
21	Su R, Jin C, Zhou L, Cao Y, Kuang M, Li L and Xiang J: Construction of a ceRNA network of hub genes affecting immune infiltration in ovarian cancer identified by WGCNA. BMC Cancer. 21:9702021. View Article : Google Scholar : PubMed/NCBI
22	Lewinsky H, Gunes EG, David K, Radomir L, Kramer MP, Pellegrino B, Perpinial M, Chen J, He TF, Mansour AG, et al: CD84 is a regulator of the immunosuppressive microenvironment in multiple myeloma. JCI Insight. 6:e1416832021.PubMed/NCBI
23	O'Connell P, Hyslop S, Blake MK, Godbehere S, Amalfitano A and Aldhamen YA: SLAMF7 Signaling reprograms t cells toward exhaustion in the tumor microenvironment. J Immunol. 206:193–205. 2021. View Article : Google Scholar : PubMed/NCBI
24	Agresta L, Hoebe KHN and Janssen EM: The emerging role of CD244 signaling in immune cells of the tumor microenvironment. Front Immunol. 9:28092018. View Article : Google Scholar : PubMed/NCBI
25	Yigit B, Wang N, Ten Hacken E, Chen SS, Bhan AK, Suarez-Fueyo A, Katsuyama E, Tsokos GC, Chiorazzi N, Wu CJ, et al: SLAMF6 as a regulator of exhausted CD8+ T cells in cancer. Cancer Immunol Res. 7:1485–1496. 2019. View Article : Google Scholar : PubMed/NCBI
26	GTEx Consortium: The genotype-tissue expression (GTEx) project. Nat Genet. 45:580–585. 2013. View Article : Google Scholar : PubMed/NCBI
27	Vivian J, Rao AA, Nothaft FA, Ketchum C, Armstrong J, Novak A, Pfeil J, Narkizian J, Deran AD, Musselman-Brown A, et al: Toil enables reproducible, open source, big biomedical data analyses. Nat Biotechnol. 35:314–316. 2017. View Article : Google Scholar : PubMed/NCBI
28	Tang Z, Kang B, Li C, Chen T and Zhang Z: GEPIA2: An enhanced web server for large-scale expression profiling and interactive analysis. Nucleic Acids Res. 47((W1)): W556–W560. 2019. View Article : Google Scholar : PubMed/NCBI
29	Chandrashekar DS, Bashel B, Balasubramanya SAH, Creighton CJ, Ponce-Rodriguez I, Chakravarthi BVSK and Varambally S: UALCAN: A portal for facilitating tumor subgroup gene expression and survival analyses. Neoplasia. 19:649–658. 2017. View Article : Google Scholar : PubMed/NCBI
30	Obuchowski NA and Bullen JA: Receiver operating characteristic (ROC) curves: Review of methods with applications in diagnostic medicine. Phys Med Biol. 63:07TR012018. View Article : Google Scholar : PubMed/NCBI
31	Lánczky A and Győrffy B: Web-based survival analysis tool tailored for medical research (KMplot): Development and implementation. J Med Internet Res. 23:e276332021. View Article : Google Scholar : PubMed/NCBI
32	Cerami E, Gao J, Dogrusoz U, Gross BE, Sumer SO, Aksoy BA, Jacobsen A, Byrne CJ, Heuer ML, Larsson E, et al: The cBio cancer genomics portal: an open platform for exploring multidimensional cancer genomics data. Cancer Discov. 2:401–404. 2012. View Article : Google Scholar : PubMed/NCBI
33	Gao J, Aksoy BA, Dogrusoz U, Dresdner G, Gross B, Sumer SO, Sun Y, Jacobsen A, Sinha R, Larsson E, et al: Integrative analysis of complex cancer genomics and clinical profiles using the cBioPortal. Sci Signal. 6:pl12013. View Article : Google Scholar : PubMed/NCBI
34	Subramanian A, Tamayo P, Mootha VK, Mukherjee S, Ebert BL, Gillette MA, Paulovich A, Pomeroy SL, Golub TR, Lander ES and Mesirov JP: Gene set enrichment analysis: A knowledge-based approach for interpreting genome-wide expression profiles. Proc Natl Acad Sci USA. 102:15545–15550. 2005. View Article : Google Scholar : PubMed/NCBI
35	Li T, Fan J, Wang B, Traugh N, Chen Q, Liu JS, Li B and Liu XS: TIMER: A web server for comprehensive analysis of tumor-infiltrating immune cells. Cancer Res. 77:e108–e110. 2017. View Article : Google Scholar : PubMed/NCBI
36	Jiang P, Gu S, Pan D, Fu J, Sahu A, Hu X, Li Z, Traugh N, Bu X, Li B, et al: Signatures of T cell dysfunction and exclusion predict cancer immunotherapy response. Nat Med. 24:1550–1558. 2018. View Article : Google Scholar : PubMed/NCBI
37	Li T, Fu J, Zeng Z, Cohen D, Li J, Chen Q, Li B and Liu XS: TIMER2.0 for analysis of tumor-infiltrating immune cells. Nucleic Acids Res. 48((W1)): W509–W514. 2020. View Article : Google Scholar : PubMed/NCBI
38	Hughes CE and Nibbs RJB: A guide to chemokines and their receptors. FEBS J. 285:2944–2971. 2018. View Article : Google Scholar : PubMed/NCBI
39	Kakinuma T and Hwang ST: Chemokines, chemokine receptors, and cancer metastasis. J Leukoc Biol. 79:639–651. 2006. View Article : Google Scholar : PubMed/NCBI
40	Kotsias F, Cebrian I and Alloatti A: Antigen processing and presentation. Int Rev Cell Mol Biol. 348:69–121. 2019. View Article : Google Scholar : PubMed/NCBI
41	Wang X, Spandidos A, Wang H and Seed B: PrimerBank: A PCR primer database for quantitative gene expression analysis, 2012 update. Nucleic Acids Res. 40((Database Issue)): D1144–D1149. 2012. View Article : Google Scholar : PubMed/NCBI
42	Wang H, Song C, Ding Y, Pan X, Ge Z, Tan BH, Gowda C, Sachdev M, Muthusami S, Ouyang H, et al: Transcriptional regulation of JARID1B/KDM5B histone demethylase by ikaros, histone deacetylase 1 (HDAC1), and casein kinase 2 (CK2) in B-cell acute lymphoblastic leukemia. J Biol Chem. 291:4004–4018. 2016. View Article : Google Scholar : PubMed/NCBI
43	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(−Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI
44	Chan BKC: Data analysis using R programming. Adv Exp Med Biol. 1082:47–122. 2018. View Article : Google Scholar : PubMed/NCBI
45	Yu G, Wang LG, Han Y and He QY: clusterProfiler: An R package for comparing biological themes among gene clusters. OMICS. 16:284–287. 2012. View Article : Google Scholar : PubMed/NCBI
46	Yoshihara K, Shahmoradgoli M, Martínez E, Vegesna R, Kim H, Torres-Garcia W, Treviño V, Shen H, Laird PW, Levine DA, et al: Inferring tumour purity and stromal and immune cell admixture from expression data. Nat Commun. 4:26122013. View Article : Google Scholar : PubMed/NCBI
47	Han Y, Liu D and Li L: PD-1/PD-L1 pathway: current researches in cancer. Am J Cancer Res. 10:727–742. 2020.PubMed/NCBI
48	Wen M, Li Y, Qin X, Qin B and Wang Q: Insight into cancer immunity: MHCs, immune cells and commensal microbiota. Cells. 12:18822023. View Article : Google Scholar : PubMed/NCBI
49	Ma R, Qu X, Che X, Yang B, Li C, Hou K, Guo T, Xiao J and Liu Y: Comparative analysis and in vitro experiments of signatures and prognostic value of immune checkpoint genes in colorectal cancer. Onco Targets Ther. 14:3517–3534. 2021. View Article : Google Scholar : PubMed/NCBI
50	Agresta L, Lehn M, Lampe K, Cantrell R, Hennies C, Szabo S, Wise-Draper T, Conforti L, Hoebe K and Janssen EM: CD244 represents a new therapeutic target in head and neck squamous cell carcinoma. J Immunother Cancer. 8:e0002452020. View Article : Google Scholar : PubMed/NCBI
51	Lewinsky H, Barak AF, Huber V, Kramer MP, Radomir L, Sever L, Orr I, Mirkin V, Dezorella N, Shapiro M, et al: CD84 regulates PD-1/PD-L1 expression and function in chronic lymphocytic leukemia. J Clin Invest. 128:5465–5478. 2018. View Article : Google Scholar : PubMed/NCBI
52	Wu D, Zhang P, Ma J, Xu J, Yang L, Xu W, Que H, Chen M and Xu H: Serum biomarker panels for the diagnosis of gastric cancer. Cancer Med. 8:1576–1583. 2019. View Article : Google Scholar : PubMed/NCBI
53	Quan Q, Xiong X, Wu S and Yu M: Identification of immune-related key genes in ovarian cancer based on WGCNA. Front Genet. 12:7602252021. View Article : Google Scholar : PubMed/NCBI
54	Veillette A and Latour S: The SLAM family of immune-cell receptors. Curr Opin Immunol. 15:277–285. 2003. View Article : Google Scholar : PubMed/NCBI
55	Wu N and Veillette A: SLAM family receptors in normal immunity and immune pathologies. Curr Opin Immunol. 38:45–51. 2016. View Article : Google Scholar : PubMed/NCBI
56	Smart JA, Oleksak JE and Hartsough EJ: Cell adhesion molecules in plasticity and metastasis. Mol Cancer Res. 19:25–37. 2021. View Article : Google Scholar : PubMed/NCBI
57	Ishihara M, Hu J, Zhang X, Choi Y, Wong A, Cano-Ruiz C, Zhao R, Tan P, Tso JL and Wu L: Comparing metastatic clear cell renal cell carcinoma model established in mouse kidney and on chicken chorioallantoic membrane. J Vis Exp. 10.3791/60314. 2020. View Article : Google Scholar
58	Fouquet G, Marcq I, Debuysscher V, Bayry J, Rabbind Singh A, Bengrine A, Nguyen-Khac E, Naassila M and Bouhlal H: Signaling lymphocytic activation molecules Slam and cancers: Friends or foes? Oncotarget. 9:16248–16262. 2018. View Article : Google Scholar : PubMed/NCBI
59	De Salort J, Sintes J, Llinàs L, Matesanz-Isabel J and Engel P: Expression of SLAM (CD150) cell-surface receptors on human B-cell subsets: From pro-B to plasma cells. Immunol Lett. 134:129–136. 2011. View Article : Google Scholar : PubMed/NCBI
60	Karampetsou MP, Comte D, Suárez-Fueyo A, Katsuyama E, Yoshida N, Kono M, Kyttaris VC and Tsokos GC: Signaling lymphocytic activation molecule family member 1 engagement inhibits T cell-B cell interaction and diminishes interleukin-6 production and plasmablast differentiation in systemic lupus erythematosus. Arthritis Rheumatol. 71:99–108. 2019. View Article : Google Scholar : PubMed/NCBI
61	Wang N, Morra M, Wu C, Gullo C, Howie D, Coyle T, Engel P and Terhorst C: CD150 is a member of a family of genes that encode glycoproteins on the surface of hematopoietic cells. Immunogenetics. 53:382–394. 2001. View Article : Google Scholar : PubMed/NCBI
62	Gordiienko I, Shlapatska L, Kholodniuk V, Sklyarenko L, Gluzman DF, Clark EA and Sidorenko SP: The interplay of CD150 and CD180 receptor pathways contribute to the pathobiology of chronic lymphocytic leukemia B cells by selective inhibition of Akt and MAPK signaling. PLoS One. 12:e01859402017. View Article : Google Scholar : PubMed/NCBI
63	Yurchenko M, Shlapatska LM, Romanets OL, Ganshevskiy D, Kashuba E, Zamoshnikova A, Ushenin YV, Snopok BA and Sidorenko SP: CD150-mediated Akt signalling pathway in normal and malignant B cells. Exp Oncol. 33:9–18. 2011.PubMed/NCBI
64	Li D, Xiong W, Wang Y, Feng J, He Y, Du J, Wang J, Yang M, Zeng H, Yang YG, et al: SLAMF3 and SLAMF4 are immune checkpoints that constrain macrophage phagocytosis of hematopoietic tumors. Sci Immunol. 7:eabj55012022.PubMed/NCBI
65	Mittal R, Wagener M, Breed ER, Liang Z, Yoseph BP, Burd EM, Farris AB III, Coopersmith CM and Ford ML: Phenotypic T cell exhaustion in a murine model of bacterial infection in the setting of pre-existing malignancy. PLoS One. 9:e935232014. View Article : Google Scholar : PubMed/NCBI
66	Bae J, Song W, Smith R, Daley J, Tai YT, Anderson KC and Munshi NC: A novel immunogenic CS1-specific peptide inducing antigen-specific cytotoxic T lymphocytes targeting multiple myeloma. Br J Haematol. 157:687–701. 2012. View Article : Google Scholar : PubMed/NCBI
67	Sugimoto A, Kataoka TR, Ito H, Kitamura K, Saito N, Hirata M, Ueshima C, Takei Y, Moriyoshi K, Otsuka Y, et al: SLAM family member 8 is expressed in and enhances the growth of anaplastic large cell lymphoma. Sci Rep. 10:25052020. View Article : Google Scholar : PubMed/NCBI
68	Zou CY, Guan GF, Zhu C, Liu TQ, Guo Q, Cheng W and Wu AH: Costimulatory checkpoint SLAMF8 is an independent prognosis factor in glioma. CNS Neurosci Ther. 25:333–342. 2019. View Article : Google Scholar : PubMed/NCBI
69	Zhang Q, Cheng L, Qin Y, Kong L, Shi X, Hu J, Li L, Ding Z, Wang T, Shen J, et al: SLAMF8 expression predicts the efficacy of anti-PD1 immunotherapy in gastrointestinal cancers. Clin Transl Immunology. 10:e13472021. View Article : Google Scholar : PubMed/NCBI
70	De Jaeghere EA, Denys HG and De Wever O: Fibroblasts fuel immune escape in the tumor microenvironment. Trends Cancer. 5:704–723. 2019. View Article : Google Scholar : PubMed/NCBI
71	Langhans B, Nischalke HD, Krämer B, Dold L, Lutz P, Mohr R, Vogt A, Toma M, Eis-Hübinger AM, Nattermann J, et al: Role of regulatory T cells and checkpoint inhibition in hepatocellular carcinoma. Cancer Immunol Immunother. 68:2055–2066. 2019. View Article : Google Scholar : PubMed/NCBI
72	Sumitomo R, Hirai T, Fujita M, Murakami H, Otake Y and Huang CL: M2 tumor-associated macrophages promote tumor progression in non-small-cell lung cancer. Exp Ther Med. 18:4490–4498. 2019.PubMed/NCBI
73	Tu D, Dou J, Wang M, Zhuang H and Zhang X: M2 macrophages contribute to cell proliferation and migration of breast cancer. Cell Biol Int. 45:831–838. 2021. View Article : Google Scholar : PubMed/NCBI
74	Wu X, Gu Z, Chen Y, Chen B, Chen W, Weng L and Liu X: Application of PD-1 blockade in cancer immunotherapy. Comput Struct Biotechnol J. 17:661–674. 2019. View Article : Google Scholar : PubMed/NCBI
75	Ai L, Xu A and Xu J: Roles of PD-1/PD-L1 pathway: Signaling, cancer, and beyond. Adv Exp Med Biol. 1248:33–59. 2020. View Article : Google Scholar : PubMed/NCBI
76	Kohli K, Pillarisetty VG and Kim TS: Key chemokines direct migration of immune cells in solid tumors. Cancer Gene Ther. 29:10–21. 2022. View Article : Google Scholar : PubMed/NCBI
77	Marcuzzi E, Angioni R, Molon B and Calì B: Chemokines and chemokine receptors: Orchestrating tumor metastasization. Int J Mol Sci. 20:962018. View Article : Google Scholar : PubMed/NCBI
78	Dai S, Zeng H, Liu Z, Jin K, Jiang W, Wang Z, Lin Z, Xiong Y, Wang J, Chang Y, et al: Intratumoral CXCL13+CD8+T cell infiltration determines poor clinical outcomes and immunoevasive contexture in patients with clear cell renal cell carcinoma. J Immunother Cancer. 9:e0018232021. View Article : Google Scholar : PubMed/NCBI
79	Zhang L, Zhang M, Wang L, Li J, Yang T, Shao Q, Liang X, Ma M, Zhang N, Jing M, et al: Identification of CCL4 as an immune-related prognostic biomarker associated with tumor proliferation and the tumor microenvironment in clear cell renal cell carcinoma. Front Oncol. 11:6946642021. View Article : Google Scholar : PubMed/NCBI
80	Lin J, Yu M, Xu X, Wang Y, Xing H, An J, Yang J, Tang C, Sun D and Zhu Y: Identification of biomarkers related to CD8+ T cell infiltration with gene co-expression network in clear cell renal cell carcinoma. Aging (Albany NY). 12:3694–3712. 2020. View Article : Google Scholar : PubMed/NCBI