Current state and challenges of emerging biomarkers for immunotherapy in hepatocellular carcinoma (Review)
- Authors:
- Mo Cheng
- Xiufeng Zheng
- Jing Wei
- Ming Liu
-
Affiliations: Department of Medical Oncology, Gastric Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P.R. China - Published online on: November 3, 2023 https://doi.org/10.3892/etm.2023.12285
- Article Number: 586
-
Copyright: © Cheng et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
This article is mentioned in:
Abstract
 |
|
Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A and Bray F: Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 71:209–249. 2021.PubMed/NCBI View Article : Google Scholar | |
|
Zhu AX, Dayyani F, Yen CJ, Ren Z, Bai Y, Meng Z, Pan H, Dillon P, Mhatre SK, Gaillard VE, et al: Alpha-fetoprotein as a potential surrogate biomarker for atezolizumab + bevacizumab treatment of hepatocellular carcinoma. Clin Cancer Res. 28:3537–3545. 2022.PubMed/NCBI View Article : Google Scholar | |
|
Llovet JM, Kelley RK, Villanueva A, Singal AG, Pikarsky E, Roayaie S, Lencioni R, Koike K, Zucman-Rossi J and Finn RS: Hepatocellular carcinoma. Nat Rev Dis Primers. 7(6)2021.PubMed/NCBI View Article : Google Scholar | |
|
Anwanwan D, Singh SK, Singh S, Saikam V and Singh R: Challenges in liver cancer and possible treatment approaches. Biochim Biophys Acta Rev Cancer. 1873(188314)2020.PubMed/NCBI View Article : Google Scholar | |
|
Zheng C, Zheng L, Yoo JK, Guo H, Zhang Y, Guo X, Kang B, Hu R, Huang JY, Zhang Q, et al: Landscape of infiltrating T cells in liver cancer revealed by single-cell sequencing. Cell. 169:1342–1356.e16. 2017.PubMed/NCBI View Article : Google Scholar | |
|
Wei SC, Duffy CR and Allison JP: Fundamental mechanisms of immune checkpoint blockade therapy. Cancer Discov. 8:1069–1086. 2018.PubMed/NCBI View Article : Google Scholar | |
|
Finn RS, Qin S, Ikeda M, Galle PR, Ducreux M, Kim TY, Kudo M, Breder V, Merle P, Kaseb AO, et al: Atezolizumab plus bevacizumab in unresectable hepatocellular carcinoma. N Engl J Med. 382:1894–1905. 2020.PubMed/NCBI View Article : Google Scholar | |
|
Zayac A and Almhanna K: Hepatobiliary cancers and immunotherapy: Where are we now and where are we heading? Transl Gastroenterol Hepatol. 5(8)2020.PubMed/NCBI View Article : Google Scholar | |
|
Ding X, He M, Chan A, Song QX, Sze SC, Chen H, Man MKH, Man K, Chan SL, Lai PBS, et al: Genomic and epigenomic features of primary and recurrent hepatocellular carcinomas. Gastroenterology. 157:1630–1645.e6. 2019.PubMed/NCBI View Article : Google Scholar | |
|
Finn RS, Ryoo BY, Merle P, Kudo M, Bouattour M, Lim HY, Breder V, Edeline J, Chao Y, Ogasawara S, et al: Pembrolizumab as second-line therapy in patients with advanced hepatocellular carcinoma in KEYNOTE-240: A randomized, double-blind, phase III trial. J Clin Oncol. 38:193–202. 2020.PubMed/NCBI View Article : Google Scholar | |
|
Yau T, Park JW, Finn RS, Cheng AL, Mathurin P, Edeline J, Kudo M, Harding JJ, Merle P, Rosmorduc O, et al: Nivolumab versus sorafenib in advanced hepatocellular carcinoma (CheckMate 459): A randomised, multicentre, open-label, phase 3 trial. Lancet Oncol. 23:77–90. 2022.PubMed/NCBI View Article : Google Scholar | |
|
Ren Z, Xu J, Bai Y, Xu A, Cang S, Du C, Li Q, Lu Y, Chen Y, Guo Y, et al: Sintilimab plus a bevacizumab biosimilar (IBI305) versus sorafenib in unresectable hepatocellular carcinoma (ORIENT-32): A randomised, open-label, phase 2-3 study. Lancet Oncol. 22:977–990. 2021.PubMed/NCBI View Article : Google Scholar | |
|
Kudo M: Durvalumab plus tremelimumab in unresectable hepatocellular carcinoma. Hepatobiliary Surg Nutr. 11:592–596. 2022.PubMed/NCBI View Article : Google Scholar | |
|
Sangro B, Melero I, Wadhawan S, Finn RS, Abou-Alfa GK, Cheng AL, Yau T, Furuse J, Park JW, Boyd Z, et al: Association of inflammatory biomarkers with clinical outcomes in nivolumab-treated patients with advanced hepatocellular carcinoma. J Hepatol. 73:1460–1469. 2020.PubMed/NCBI View Article : Google Scholar | |
|
Zhu AX, Finn RS, Edeline J, Cattan S, Ogasawara S, Palmer D, Verslype C, Zagonel V, Fartoux L, Vogel A, et al: Pembrolizumab in patients with advanced hepatocellular carcinoma previously treated with sorafenib (KEYNOTE-224): A non-randomised, open-label phase 2 trial. Lancet Oncol. 19:940–952. 2018.PubMed/NCBI View Article : Google Scholar | |
|
Ho WJ, Danilova L, Lim SJ, Verma R, Xavier S, Leatherman JM, Sztein MB, Fertig EJ, Wang H, Jaffee E and Yarchoan M: Viral status, immune microenvironment and immunological response to checkpoint inhibitors in hepatocellular carcinoma. J Immunother Cancer. 8(e000394)2020.PubMed/NCBI View Article : Google Scholar | |
|
Avgerinos KI, Spyrou N, Mantzoros CS and Dalamaga M: Obesity and cancer risk: Emerging biological mechanisms and perspectives. Metabolism. 92:121–135. 2019.PubMed/NCBI View Article : Google Scholar | |
|
Ringel AE, Drijvers JM, Baker GJ, Catozzi A, García-Cañaveras JC, Gassaway BM, Miller BC, Juneja VR, Nguyen TH, Joshi S, et al: Obesity shapes metabolism in the tumor microenvironment to suppress anti-tumor immunity. Cell. 183:1848–1866.e26. 2020.PubMed/NCBI View Article : Google Scholar | |
|
Akce M, Liu Y, Zakka K, Martini DJ, Draper A, Alese OB, Shaib WL, Wu C, Wedd JP, Sellers MT, et al: Impact of sarcopenia, BMI, and inflammatory biomarkers on survival in advanced hepatocellular carcinoma treated with anti-PD-1 antibody. Am J Clin Oncol. 44:74–81. 2021.PubMed/NCBI View Article : Google Scholar | |
|
Bellissimo F, Pinzone MR, Cacopardo B and Nunnari G: Diagnostic and therapeutic management of hepatocellular carcinoma. World J Gastroenterol. 21:12003–12021. 2015.PubMed/NCBI View Article : Google Scholar | |
|
Tsuchiya N, Sawada Y, Endo I, Saito K, Uemura Y and Nakatsura T: Biomarkers for the early diagnosis of hepatocellular carcinoma. World J Gastroenterol. 21:10573–10583. 2015.PubMed/NCBI View Article : Google Scholar | |
|
Cao W, Chen Y, Han W, Yuan J, Xie W, Liu K, Qiu Y, Wang X and Li X: Potentiality of α-fetoprotein (AFP) and soluble intercellular adhesion molecule-1 (sICAM-1) in prognosis prediction and immunotherapy response for patients with hepatocellular carcinoma. Bioengineered. 12:9435–9451. 2021.PubMed/NCBI View Article : Google Scholar | |
|
Spahn S, Roessler D, Pompilia R, Gabernet G, Gladstone BP, Horger M, Biskup S, Feldhahn M, Nahnsen S, Hilke FJ, et al: Clinical and genetic tumor characteristics of responding and non-responding patients to PD-1 inhibition in hepatocellular carcinoma. Cancers (Basel). 12(3830)2020.PubMed/NCBI View Article : Google Scholar | |
|
Sun X, Mei J, Lin W, Yang Z, Peng W, Chen J, Zhang Y, Xu L and Chen M: Reductions in AFP and PIVKA-II can predict the efficiency of anti-PD-1 immunotherapy in HCC patients. BMC Cancer. 21(775)2021.PubMed/NCBI View Article : Google Scholar | |
|
Hatanaka T, Kakizaki S, Hiraoka A, Tada T, Hirooka M, Kariyama K, Tani J, Atsukawa M, Takaguchi K, Itobayashi E, et al: Prognostic impact of C-reactive protein and alpha-fetoprotein in immunotherapy score in hepatocellular carcinoma patients treated with atezolizumab plus bevacizumab: A multicenter retrospective study. Hepatol Int. 16:1150–1160. 2022.PubMed/NCBI View Article : Google Scholar | |
|
Scheiner B, Pomej K, Kirstein MM, Hucke F, Finkelmeier F, Waidmann O, Himmelsbach V, Schulze K, von Felden J, Fründt TW, et al: Prognosis of patients with hepatocellular carcinoma treated with immunotherapy-development and validation of the CRAFITY score. J Hepatol. 76:353–363. 2022.PubMed/NCBI View Article : Google Scholar | |
|
Guan R, Mei J, Lin W, Deng M, Li S and Guo R: Is the CRAFITY score a superior predictor of prognosis and adverse events in hepatocellular carcinoma patients treated with locoregional-immunotherapy? Hepatol Int. 17:1279–1288. 2023.PubMed/NCBI View Article : Google Scholar | |
|
Yang M, Pan Y and Wang W: Prognostic significance of the CRAFITY score in hepatocellular carcinoma treated with immunotherapy: A systematic review and meta-analysis. BMC Cancer. 23(236)2023.PubMed/NCBI View Article : Google Scholar | |
|
Dharmapuri S, Özbek U, Lin JY, Sung M, Schwartz M, Branch AD and Ang C: Predictive value of neutrophil to lymphocyte ratio and platelet to lymphocyte ratio in advanced hepatocellular carcinoma patients treated with anti-PD-1 therapy. Cancer Med. 9:4962–4970. 2020.PubMed/NCBI View Article : Google Scholar | |
|
Muhammed A, Fulgenzi CAM, Dharmapuri S, Pinter M, Balcar L, Scheiner B, Marron TU, Jun T, Saeed A, Hildebrand H, et al: The systemic inflammatory response identifies patients with adverse clinical outcome from immunotherapy in hepatocellular carcinoma. Cancers (Basel). 14(186)2021.PubMed/NCBI View Article : Google Scholar | |
|
Ochi H, Kurosaki M, Joko K, Mashiba T, Tamaki N, Tsuchiya K, Marusawa H, Tada T, Nakamura S, Narita R, et al: Usefulness of neutrophil-to-lymphocyte ratio in predicting progression and survival outcomes after atezolizumab-bevacizumab treatment for hepatocellular carcinoma. Hepatol Res. 53:61–71. 2023.PubMed/NCBI View Article : Google Scholar | |
|
Jeon SH, Lee YJ, Kim HD, Nam H, Ryoo BY, Park SH, Yoo C and Shin EC: Dynamic changes in peripheral blood monocytes early after anti-PD-1 therapy predict clinical outcomes in hepatocellular carcinoma. Cancer Immunol Immunother. 72:371–384. 2023.PubMed/NCBI View Article : Google Scholar | |
|
Riedl JM, Barth DA, Brueckl WM, Zeitler G, Foris V, Mollnar S, Stotz M, Rossmann CH, Terbuch A, Balic M, et al: C-reactive protein (CRP) levels in immune checkpoint inhibitor response and progression in advanced non-small cell lung cancer: A Bi-center study. Cancers (Basel). 12(2319)2020.PubMed/NCBI View Article : Google Scholar | |
|
Klümper N, Saal J, Berner F, Lichtensteiger C, Wyss N, Heine A, Bauernfeind FG, Ellinger J, Brossart P, Diem S, et al: C reactive protein flare predicts response to checkpoint inhibitor treatment in non-small cell lung cancer. J Immunother Cancer. 10(e004024)2022.PubMed/NCBI View Article : Google Scholar | |
|
Ramsey S: The role of the systemic inflammatory response as a biomarker in immunotherapy for renal cell cancer. Mol Diagn Ther. 13:277–281. 2009.PubMed/NCBI View Article : Google Scholar | |
|
Chung MW, Kim MJ, Won EJ, Lee YJ, Yun YW, Cho SB, Joo YE, Hwang JE, Bae WK, Chung IJ, et al: Gut microbiome composition can predict the response to nivolumab in advanced hepatocellular carcinoma patients. World J Gastroenterol. 27:7340–7349. 2021.PubMed/NCBI View Article : Google Scholar | |
|
Mao J, Wang D, Long J, Yang X, Lin J, Song Y, Xie F, Xun Z, Wang Y, Wang Y, et al: Gut microbiome is associated with the clinical response to anti-PD-1 based immunotherapy in hepatobiliary cancers. J Immunother Cancer. 9(e003334)2021.PubMed/NCBI View Article : Google Scholar | |
|
Zhang L, Wu YN, Chen T, Ren CH, Li X and Liu GX: Relationship between intestinal microbial dysbiosis and primary liver cancer. Hepatobiliary Pancreat Dis Int. 18:149–157. 2019.PubMed/NCBI View Article : Google Scholar | |
|
Schwabe RF and Greten TF: Gut microbiome in HCC-mechanisms, diagnosis and therapy. J Hepatol. 72:230–238. 2020.PubMed/NCBI View Article : Google Scholar | |
|
Temraz S, Nassar F, Kreidieh F, Mukherji D, Shamseddine A and Nasr R: Hepatocellular carcinoma immunotherapy and the potential influence of gut microbiome. Int J Mol Sci. 22(7800)2021.PubMed/NCBI View Article : Google Scholar | |
|
Dapito DH, Mencin A, Gwak GY, Pradere JP, Jang MK, Mederacke I, Caviglia JM, Khiabanian H, Adeyemi A, Bataller R, et al: Promotion of hepatocellular carcinoma by the intestinal microbiota and TLR4. Cancer Cell. 21:504–516. 2012.PubMed/NCBI View Article : Google Scholar | |
|
Peng X, Gong C, Zhang W and Zhou A: Advanced development of biomarkers for immunotherapy in hepatocellular carcinoma. Front Oncol. 12(1091088)2023.PubMed/NCBI View Article : Google Scholar | |
|
Vaisman-Mentesh A, Gutierrez-Gonzalez M, DeKosky BJ and Wine Y: The molecular mechanisms that underlie the immune biology of anti-drug antibody formation following treatment with monoclonal antibodies. Front Immunol. 11(1951)2020.PubMed/NCBI View Article : Google Scholar | |
|
Davda J, Declerck P, Hu-Lieskovan S, Hickling TP, Jacobs IA, Chou J, Salek-Ardakani S and Kraynov E: Immunogenicity of immunomodulatory, antibody-based, oncology therapeutics. J Immunother Cancer. 7(105)2019.PubMed/NCBI View Article : Google Scholar | |
|
Enrico D, Paci A, Chaput N, Karamouza E and Besse B: Antidrug antibodies against immune checkpoint blockers: Impairment of drug efficacy or indication of immune activation? Clin Cancer Res. 26:787–792. 2020.PubMed/NCBI View Article : Google Scholar | |
|
Kim C, Yang H, Kim I, Kang B, Kim H, Kim H, Lee WS, Jung S, Lim HY, Cheon J and Chon HJ: Association of high levels of antidrug antibodies against atezolizumab with clinical outcomes and T-cell responses in patients with hepatocellular carcinoma. JAMA Oncol. 8:1825–1829. 2022.PubMed/NCBI View Article : Google Scholar | |
|
Peters S, Galle PR, Bernaards CA, Ballinger M, Bruno R, Quarmby V, Ruppel J, Vilimovskij A, Wu B, Sternheim N and Reck M: Evaluation of atezolizumab immunogenicity: Efficacy and safety (Part 2). Clin Transl Sci. 15:141–157. 2022.PubMed/NCBI View Article : Google Scholar | |
|
Myler H, Pedras-Vasconcelos J, Phillips K, Hottenstein CS, Chamberlain P, Devanaryan V, Gleason C, Goodman J, Manning MS, Purushothama S, et al: Anti-drug antibody validation testing and reporting harmonization. AAPS J. 24(4)2021.PubMed/NCBI View Article : Google Scholar | |
|
Sadreddini S, Baradaran B, Aghebati-Maleki A, Sadreddini S, Shanehbandi D, Fotouhi A and Aghebati-Maleki L: Immune checkpoint blockade opens a new way to cancer immunotherapy. J Cell Physiol. 234:8541–8549. 2019.PubMed/NCBI View Article : Google Scholar | |
|
Pardoll DM: The blockade of immune checkpoints in cancer immunotherapy. Nat Rev Cancer. 12:252–264. 2012.PubMed/NCBI View Article : Google Scholar | |
|
Kwok G, Yau TC, Chiu JW, Tse E and Kwong YL: Pembrolizumab (Keytruda). Hum Vaccin Immunother. 12:2777–2789. 2016.PubMed/NCBI View Article : Google Scholar | |
|
Beaver JA, Hazarika M, Mulkey F, Mushti S, Chen H, He K, Sridhara R, Goldberg KB, Chuk MK, Chi DC, et al: Patients with melanoma treated with an anti-PD-1 antibody beyond RECIST progression: A US food and drug administration pooled analysis. Lancet Oncol. 19:229–239. 2018.PubMed/NCBI View Article : Google Scholar | |
|
Ailia MJ, Heo J and Yoo SY: Navigating through the PD-1/PDL-1 landscape: A systematic review and meta-analysis of clinical outcomes in hepatocellular carcinoma and their influence on immunotherapy and tumor microenvironment. Int J Mol Sci. 24(6495)2023.PubMed/NCBI View Article : Google Scholar | |
|
Zhu AX, Abbas AR, de Galarreta MR, Guan Y, Lu S, Koeppen H, Zhang W, Hsu CH, He AR, Ryoo BY, et al: Molecular correlates of clinical response and resistance to atezolizumab in combination with bevacizumab in advanced hepatocellular carcinoma. Nat Med. 28:1599–1611. 2022.PubMed/NCBI View Article : Google Scholar | |
|
Paver EC, Cooper WA, Colebatch AJ, Ferguson PM, Hill SK, Lum T, Shin JS, O'Toole S, Anderson L, Scolyer RA and Gupta R: Programmed death ligand-1 (PD-L1) as a predictive marker for immunotherapy in solid tumours: A guide to immunohistochemistry implementation and interpretation. Pathology. 53:141–156. 2021.PubMed/NCBI View Article : Google Scholar | |
|
Doroshow DB, Bhalla S, Beasley MB, Sholl LM, Kerr KM, Gnjatic S, Wistuba II, Rimm DL, Tsao MS and Hirsch FR: PD-L1 as a biomarker of response to immune-checkpoint inhibitors. Nat Rev Clin Oncol. 18:345–362. 2021.PubMed/NCBI View Article : Google Scholar | |
|
Dong ZY, Wu SP, Liao RQ, Huang SM and Wu YL: Potential biomarker for checkpoint blockade immunotherapy and treatment strategy. Tumour Biol. 37:4251–4261. 2016.PubMed/NCBI View Article : Google Scholar | |
|
Kim MS, Xu A, Haslam A and Prasad V: Quality of biomarker defined subgroups in FDA approvals of PD-1/PD-L1 inhibitors 2014 to 2020. Int J Cancer. 150:1905–1910. 2022.PubMed/NCBI View Article : Google Scholar | |
|
He S and Tang S: WNT/β-catenin signaling in the development of liver cancers. Biomed Pharmacother. 132(110851)2020.PubMed/NCBI View Article : Google Scholar | |
|
Perugorria MJ, Olaizola P, Labiano I, Esparza-Baquer A, Marzioni M, Marin JJG, Bujanda L and Banales JM: Wnt-β-catenin signalling in liver development, health and disease. Nat Rev Gastroenterol Hepatol. 16:121–136. 2019.PubMed/NCBI View Article : Google Scholar | |
|
Llovet JM, Montal R, Sia D and Finn RS: Molecular therapies and precision medicine for hepatocellular carcinoma. Nat Rev Clin Oncol. 15:599–616. 2018.PubMed/NCBI View Article : Google Scholar | |
|
Pinyol R, Sia D and Llovet JM: Immune exclusion-Wnt/CTNNB1 class predicts resistance to immunotherapies in HCC. Clin Cancer Res. 25:2021–2023. 2019.PubMed/NCBI View Article : Google Scholar | |
|
Ruiz de Galarreta M, Bresnahan E, Molina-Sánchez P, Lindblad KE, Maier B, Sia D, Puigvehi M, Miguela V, Casanova-Acebes M, Dhainaut M, et al: β-catenin activation promotes immune escape and resistance to anti-PD-1 therapy in hepatocellular carcinoma. Cancer Discov. 9:1124–1141. 2019.PubMed/NCBI View Article : Google Scholar | |
|
Harding JJ, Nandakumar S, Armenia J, Khalil DN, Albano M, Ly M, Shia J, Hechtman JF, Kundra R, El Dika I, et al: Prospective genotyping of hepatocellular carcinoma: Clinical implications of next-generation sequencing for matching patients to targeted and immune therapies. Clin Cancer Res. 25:2116–2126. 2019.PubMed/NCBI View Article : Google Scholar | |
|
Wang Z, Sheng YY, Gao XM, Wang CQ, Wang XY, Lu XU, Wei JW, Zhang KL, Dong QZ and Qin LX: β-catenin mutation is correlated with a favorable prognosis in patients with hepatocellular carcinoma. Mol Clin Oncol. 3:936–940. 2015.PubMed/NCBI View Article : Google Scholar | |
|
Chen L, Zhou Q, Liu J and Zhang W: CTNNB1 alternation is a potential biomarker for immunotherapy prognosis in patients with hepatocellular carcinoma. Front Immunol. 12(759565)2021.PubMed/NCBI View Article : Google Scholar | |
|
Caja L, Dituri F, Mancarella S, Caballero-Diaz D, Moustakas A, Giannelli G and Fabregat I: TGF-β and the tissue microenvironment: Relevance in fibrosis and cancer. Int J Mol Sci. 19(1294)2018.PubMed/NCBI View Article : Google Scholar | |
|
Chen J, Gingold JA and Su X: Immunomodulatory TGF-β signaling in hepatocellular carcinoma. Trends Mol Med. 25:1010–1023. 2019.PubMed/NCBI View Article : Google Scholar | |
|
Mariathasan S, Turley SJ, Nickles D, Castiglioni A, Yuen K, Wang Y, Kadel EE III, Koeppen H, Astarita JL, Cubas R, et al: TGFβ attenuates tumour response to PD-L1 blockade by contributing to exclusion of T cells. Nature. 554:544–548. 2018.PubMed/NCBI View Article : Google Scholar | |
|
Horn LA, Chariou PL, Gameiro SR, Qin H, Iida M, Fousek K, Meyer TJ, Cam M, Flies D, Langermann S, et al: Remodeling the tumor microenvironment via blockade of LAIR-1 and TGF-β signaling enables PD-L1-mediated tumor eradication. J Clin Invest. 132(e155148)2022.PubMed/NCBI View Article : Google Scholar | |
|
Wu ZH, Yang DL, Wang L and Liu J: Epigenetic and immune-cell infiltration changes in the tumor microenvironment in hepatocellular carcinoma. Front Immunol. 12(793343)2021.PubMed/NCBI View Article : Google Scholar | |
|
Dai Y, Qiang W, Lin K, Gui Y, Lan X and Wang D: An immune-related gene signature for predicting survival and immunotherapy efficacy in hepatocellular carcinoma. Cancer Immunol Immunother. 70:967–979. 2021.PubMed/NCBI View Article : Google Scholar | |
|
Klempner SJ, Fabrizio D, Bane S, Reinhart M, Peoples T, Ali SM, Sokol ES, Frampton G, Schrock AB, Anhorn R and Reddy P: Tumor mutational burden as a predictive biomarker for response to immune checkpoint inhibitors: A review of current evidence. Oncologist. 25:e147–e159. 2020.PubMed/NCBI View Article : Google Scholar | |
|
Samstein RM, Lee CH, Shoushtari AN, Hellmann MD, Shen R, Janjigian YY, Barron DA, Zehir A, Jordan EJ, Omuro A, et al: Tumor mutational load predicts survival after immunotherapy across multiple cancer types. Nat Genet. 51:202–206. 2019.PubMed/NCBI View Article : Google Scholar | |
|
Marabelle A, Fakih M, Lopez J, Shah M, Shapira-Frommer R, Nakagawa K, Chung HC, Kindler HL, Lopez-Martin JA, Miller WH Jr, et al: Association of tumour mutational burden with outcomes in patients with advanced solid tumours treated with pembrolizumab: Prospective biomarker analysis of the multicohort, open-label, phase 2 KEYNOTE-158 study. Lancet Oncol. 21:1353–1365. 2020.PubMed/NCBI View Article : Google Scholar | |
|
Xu J, Zhang Y, Jia R, Yue C, Chang L, Liu R, Zhang G, Zhao C, Zhang Y, Chen C, et al: Anti-PD-1 antibody SHR-1210 combined with apatinib for advanced hepatocellular carcinoma, gastric, or esophagogastric junction cancer: An open-label, dose escalation and expansion study. Clin Cancer Res. 25:515–523. 2019.PubMed/NCBI View Article : Google Scholar | |
|
Ang C, Klempner SJ, Ali SM, Madison R, Ross JS, Severson EA, Fabrizio D, Goodman A, Kurzrock R, Suh J and Millis SZ: Prevalence of established and emerging biomarkers of immune checkpoint inhibitor response in advanced hepatocellular carcinoma. Oncotarget. 10:4018–4025. 2019.PubMed/NCBI View Article : Google Scholar | |
|
Eso Y, Shimizu T, Takeda H, Takai A and Marusawa H: Microsatellite instability and immune checkpoint inhibitors: Toward precision medicine against gastrointestinal and hepatobiliary cancers. J Gastroenterol. 55:15–26. 2020.PubMed/NCBI View Article : Google Scholar | |
|
Malapelle U, Parente P, Pepe F, De Luca C, Pisapia P, Sgariglia R, Nacchio M, Gragnano G, Russo G, Conticelli F, et al: Evaluation of micro satellite instability and mismatch repair status in different solid tumors: A multicenter analysis in a real world setting. Cells. 10(1878)2021.PubMed/NCBI View Article : Google Scholar | |
|
Cohen R, Hain E, Buhard O, Guilloux A, Bardier A, Kaci R, Bertheau P, Renaud F, Bibeau F, Fléjou JF, et al: Association of primary resistance to immune checkpoint inhibitors in metastatic colorectal cancer with misdiagnosis of microsatellite instability or mismatch repair deficiency status. JAMA Oncol. 5:551–555. 2019.PubMed/NCBI View Article : Google Scholar | |
|
Marcus L, Lemery SJ, Keegan P and Pazdur R: FDA approval summary: Pembrolizumab for the treatment of microsatellite instability-high solid tumors. Clin Cancer Res. 25:3753–3758. 2019.PubMed/NCBI View Article : Google Scholar | |
|
Prasad V, Kaestner V and Mailankody S: Cancer drugs approved based on biomarkers and not tumor Type-FDA approval of pembrolizumab for mismatch repair-deficient solid cancers. JAMA Oncol. 4:157–158. 2018.PubMed/NCBI View Article : Google Scholar | |
|
Bonneville R, Krook MA, Kautto EA, Miya J, Wing MR, Chen HZ, Reeser JW, Yu L and Roychowdhury S: Landscape of microsatellite instability across 39 cancer types. JCO Precis Oncol. 2017(PO.17.00073)2017.PubMed/NCBI View Article : Google Scholar | |
|
Kawaoka T, Ando Y, Yamauchi M, Suehiro Y, Yamaoka K, Kosaka Y, Fuji Y, Uchikawa S, Morio K, Fujino H, et al: Incidence of microsatellite instability-high hepatocellular carcinoma among Japanese patients and response to pembrolizumab. Hepatol Res. 50:885–888. 2020.PubMed/NCBI View Article : Google Scholar | |
|
Ando Y, Yamauchi M, Suehiro Y, Yamaoka K, Kosaka Y, Fuji Y, Uchikawa S, Kodama K, Morio K, Fujino H, et al: Complete response to pembrolizumab in advanced hepatocellular carcinoma with microsatellite instability. Clin J Gastroenterol. 13:867–872. 2020.PubMed/NCBI View Article : Google Scholar | |
|
Mukai S, Kanzaki H, Ogasawara S, Ishino T, Ogawa K, Nakagawa M, Fujiwara K, Unozawa H, Iwanaga T, Sakuma T, et al: Exploring microsatellite instability in patients with advanced hepatocellular carcinoma and its tumor microenvironment. JGH Open. 5:1266–1274. 2021.PubMed/NCBI View Article : Google Scholar | |
|
Buchler T: Microsatellite instability and metastatic colorectal cancer-a clinical perspective. Front Oncol. 12(888181)2022.PubMed/NCBI View Article : Google Scholar | |
|
Cercek A, Lumish M, Sinopoli J, Weiss J, Shia J, Lamendola-Essel M, El Dika IH, Segal N, Shcherba M, Sugarman R, et al: PD-1 blockade in mismatch repair-deficient, locally advanced rectal cancer. N Engl J Med. 386:2363–2376. 2022.PubMed/NCBI View Article : Google Scholar | |
|
Turner KM, Delman AM, Wima K, Quillin RC, Shah SA, Ahmad SA, Patel SH and Wilson GC: Microsatellite instability is associated with worse overall survival in resectable colorectal liver metastases. Am J Surg. 225:322–327. 2023.PubMed/NCBI View Article : Google Scholar | |
|
Wu T and Dai Y: Tumor microenvironment and therapeutic response. Cancer Lett. 387:61–68. 2017.PubMed/NCBI View Article : Google Scholar | |
|
Oura K, Morishita A, Tani J and Masaki T: Tumor immune microenvironment and immunosuppressive therapy in hepatocellular carcinoma: A review. Int J Mol Sci. 22(5801)2021.PubMed/NCBI View Article : Google Scholar | |
|
Zheng X, Jin W, Wang S and Ding H: Progression on the roles and mechanisms of tumor-infiltrating T lymphocytes in patients with hepatocellular carcinoma. Front Immunol. 12(729705)2021.PubMed/NCBI View Article : Google Scholar | |
|
Xu X, Tan Y, Qian Y, Xue W, Wang Y, Du J, Jin L and Ding W: Clinicopathologic and prognostic significance of tumor-infiltrating CD8+ T cells in patients with hepatocellular carcinoma: A meta-analysis. Medicine (Baltimore). 98(e13923)2019.PubMed/NCBI View Article : Google Scholar | |
|
El-Khoueiry AB, Sangro B, Yau T, Crocenzi TS, Kudo M, Hsu C, Kim TY, Choo SP, Trojan J, Welling TH Rd, et al: Nivolumab in patients with advanced hepatocellular carcinoma (CheckMate 040): An open-label, non-comparative, phase 1/2 dose escalation and expansion trial. Lancet. 389:2492–2502. 2017.PubMed/NCBI View Article : Google Scholar | |
|
Wang C, Singer M and Anderson AC: Molecular dissection of CD8(+) T-cell dysfunction. Trends Immunol. 38:567–576. 2017.PubMed/NCBI View Article : Google Scholar | |
|
Ma J, Zheng B, Goswami S, Meng L, Zhang D, Cao C, Li T, Zhu F, Ma L, Zhang Z, et al: PD1Hi CD8+ T cells correlate with exhausted signature and poor clinical outcome in hepatocellular carcinoma. J Immunother Cancer. 7(331)2019.PubMed/NCBI View Article : Google Scholar | |
|
Ng HHM, Lee RY, Goh S, Tay ISY, Lim X, Lee B, Chew V, Li H, Tan B, Lim S, et al: Immunohistochemical scoring of CD38 in the tumor microenvironment predicts responsiveness to anti-PD-1/PD-L1 immunotherapy in hepatocellular carcinoma. J Immunother Cancer. 8(e000987)2020.PubMed/NCBI View Article : Google Scholar | |
|
Gu X, Guan J, Xu J, Zheng Q, Chen C, Yang Q, Huang C, Wang G, Zhou H, Chen Z and Zhu H: Model based on five tumour immune microenvironment-related genes for predicting hepatocellular carcinoma immunotherapy outcomes. J Transl Med. 19(26)2021.PubMed/NCBI View Article : Google Scholar | |
|
Maravelia P, Silva DN, Rovesti G, Chrobok M, Stål P, Lu YC and Pasetto A: Liquid biopsy in hepatocellular carcinoma: Opportunities and challenges for immunotherapy. Cancers (Basel). 13(4334)2021.PubMed/NCBI View Article : Google Scholar | |
|
Cheng F, Su L and Qian C: Circulating tumor DNA: A promising biomarker in the liquid biopsy of cancer. Oncotarget. 7:48832–48841. 2016.PubMed/NCBI View Article : Google Scholar | |
|
Cabel L, Riva F, Servois V, Livartowski A, Daniel C, Rampanou A, Lantz O, Romano E, Milder M, Buecher B, et al: Circulating tumor DNA changes for early monitoring of anti-PD1 immunotherapy: A proof-of-concept study. Ann Oncol. 28:1996–2001. 2017.PubMed/NCBI View Article : Google Scholar | |
|
Peng Y, Mei W, Ma K and Zeng C: Circulating tumor DNA and minimal residual disease (MRD) in solid tumors: Current horizons and future perspectives. Front Oncol. 11(763790)2021.PubMed/NCBI View Article : Google Scholar | |
|
Winograd P, Hou S, Court CM, Lee YT, Chen PJ, Zhu Y, Sadeghi S, Finn RS, Teng PC, Wang JJ, et al: Hepatocellular carcinoma-circulating tumor cells expressing PD-L1 are prognostic and potentially associated with response to checkpoint inhibitors. Hepatol Commun. 4:1527–1540. 2020.PubMed/NCBI View Article : Google Scholar | |
|
Cheng AL, Hsu C, Chan SL, Choo SP and Kudo M: Challenges of combination therapy with immune checkpoint inhibitors for hepatocellular carcinoma. J Hepatol. 72:307–319. 2020.PubMed/NCBI View Article : Google Scholar | |
|
Lee JS and Ruppin E: Multiomics prediction of response rates to therapies to inhibit programmed cell death 1 and programmed cell death 1 ligand 1. JAMA Oncol. 5:1614–1618. 2019.PubMed/NCBI View Article : Google Scholar | |
|
Lu S, Stein JE, Rimm DL, Wang DW, Bell JM, Johnson DB, Sosman JA, Schalper KA, Anders RA, Wang H, et al: Comparison of biomarker modalities for predicting response to PD-1/PD-L1 checkpoint blockade: A systematic review and meta-analysis. JAMA Oncol. 5:1195–1204. 2019.PubMed/NCBI View Article : Google Scholar | |
|
Giraldo NA, Nguyen P, Engle EL, Kaunitz GJ, Cottrell TR, Berry S, Green B, Soni A, Cuda JD, Stein JE, et al: Multidimensional, quantitative assessment of PD-1/PD-L1 expression in patients with Merkel cell carcinoma and association with response to pembrolizumab. J Immunother Cancer. 6(99)2018.PubMed/NCBI View Article : Google Scholar | |
|
Kim H, Kwon HJ, Kim ES, Kwon S, Suh KJ, Kim SH, Kim YJ, Lee JS and Chung JH: Comparison of the predictive power of a combination versus individual biomarker testing in non-small cell lung cancer patients treated with immune checkpoint inhibitors. Cancer Res Treat. 54:424–433. 2022.PubMed/NCBI View Article : Google Scholar | |
|
Hurkmans DP, Kuipers ME, Smit J, van Marion R, Mathijssen RHJ, Postmus PE, Hiemstra PS, Aerts JGJV, von der Thüsen JH and van der Burg SH: Tumor mutational load, CD8+ T cells, expression of PD-L1 and HLA class I to guide immunotherapy decisions in NSCLC patients. Cancer Immunol Immunother. 69:771–777. 2020.PubMed/NCBI View Article : Google Scholar | |
|
Yin S, Chen Z, Chen D and Yan D: Strategies targeting PD-L1 expression and associated opportunities for cancer combination therapy. Theranostics. 13:1520–1544. 2023.PubMed/NCBI View Article : Google Scholar | |
|
Lemaire V, Shemesh CS and Rotte A: Pharmacology-based ranking of anti-cancer drugs to guide clinical development of cancer immunotherapy combinations. J Exp Clin Cancer Res. 40(311)2021.PubMed/NCBI View Article : Google Scholar | |
|
Marei HE, Hasan A, Pozzoli G and Cenciarelli C: Cancer immunotherapy with immune checkpoint inhibitors (ICIs): Potential, mechanisms of resistance, and strategies for reinvigorating T cell responsiveness when resistance is acquired. Cancer Cell Int. 23(64)2023.PubMed/NCBI View Article : Google Scholar | |
|
Pires da Silva I, Ahmed T, McQuade JL, Nebhan CA, Park JJ, Versluis JM, Serra-Bellver P, Khan Y, Slattery T, Oberoi HK, et al: Clinical models to define response and survival with anti-PD-1 antibodies alone or combined with ipilimumab in metastatic melanoma. J Clin Oncol. 40:1068–1080. 2022.PubMed/NCBI View Article : Google Scholar | |
|
Rotte A: Predictive models for response and survival in patients treated with anti-PD-1 monotherapy or with anti-PD-1 and ipilimumab combination: Editorial commentary. Ann Transl Med. 11(227)2023.PubMed/NCBI View Article : Google Scholar |
