Tumor-immune Co-evolution in hepatocellular carcinoma and its implication for immunotherapy resistance

Rooney MS, et al. Molecular and genetic properties of tumors associated with local immune cytolytic activity. Cell 2015;160(1-2): 48–61.

Lin Z, et al. Targeting tumor microenvironment as a treatment strategy for hepatocellular carcinoma. Hepatobiliary Surg Nutr 2020;9(6): 794–6.

Sangro B, et al. Advances in immunotherapy for hepatocellular carcinoma. Nat Rev Gastroenterol Hepatol 2021;18(8): 525–43.

Finn RS, et al. Atezolizumab plus bevacizumab in unresectable hepatocellular carcinoma. N Engl J Med 2020;382(20): 1894–905.

Finn RS, 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: Off J Am Soc Clin Oncol 2020;38(3): 193–202.

Yau T, et al. LBA38_PR - CheckMate 459: a randomized, multi-center phase Ⅲ study of nivolumab (NIVO) vs sorafenib (SOR) as first-line (1L) treatment in patients (pts) with advanced hepatocellular carcinoma (aHCC). Ann Oncol 2019;30: v874–5.

Pfister D, et al. NASH limits anti-tumour surveillance in immunotherapy-treated HCC. Nature 2021;592(7854): 450–6.

Ding X, et al. Genomic and epigenomic features of primary and recurrent hepatocellular carcinomas. Gastroenterology 2019;157(6): 1630–45. e6.

Friemel J, et al. Intratumor heterogeneity in hepatocellular carcinoma. Clin Cancer Res: Off J Am Assoc Canc Res 2015;21(8): 1951–61.

Craig AJ, et al. Tumour evolution in hepatocellular carcinoma. Nat Rev Gastroenterol Hepatol 2020;17(3): 139–52.

Kurebayashi Y, et al. Landscape of immune microenvironment in hepatocellular carcinoma and its additional impact on histological and molecular classification. Hepatology 2018;68(3): 1025–41.

Zheng C, et al. Landscape of infiltrating T cells in liver cancer revealed by single-cell sequencing. Cell 2017;169(7): 1342–56. e16.

Zhang Q, et al. Landscape and dynamics of single immune cells in hepatocellular carcinoma. Cell 2019;179(4).

Zhang Q, et al. Integrated multiomic analysis reveals comprehensive tumour heterogeneity and novel immunophenotypic classification in hepatocellular carcinomas. Gut 2019;68(11): 2019–31.

Ma L, et al. Tumor cell biodiversity drives microenvironmental reprogramming in liver cancer. Cancer Cell 2019;36(4): 418–30. e6.

Losic B, et al. Intratumoral heterogeneity and clonal evolution in liver cancer. Nat Commun 2020;11(1): 291.

Dong L-q, et al. Heterogeneous immunogenomic features and distinct escape mechanisms in multifocal hepatocellular carcinoma. J Hepatol 2020;72(5): 896–908.

Nguyen PHD, et al. Intratumoural immune heterogeneity as a hallmark of tumour evolution and progression in hepatocellular carcinoma. Nat Commun 2021;12(1): 227.

Ma L, et al. Single-cell atlas of tumor cell evolution in response to therapy in hepatocellular carcinoma and intrahepatic cholangiocarcinoma. J Hepatol 2021.

Pinter M, Jain RK, Duda DG. The current landscape of immune checkpoint blockade in hepatocellular carcinoma: a review. JAMA Oncol 2021;7(1): 113–23.

Kelley RK, et al. Safety, efficacy, and pharmacodynamics of tremelimumab plus durvalumab for patients with unresectable hepatocellular carcinoma: randomized expansion of a phase Ⅰ/Ⅱ study. J Clin Oncol 2021;39(27): 2991–3001.

Yau T, et al. Efficacy and safety of nivolumab plus ipilimumab in patients with advanced hepatocellular carcinoma previously treated with sorafenib: the CheckMate 040 randomized clinical trial. JAMA Oncol 2020;6(11): e204564.

Yau T, et al. Nivolumab (NIVO) þ ipilimumab (IPI) þ cabozantinib (CABO) combination therapy in patients (pts) with advanced hepatocellular carcinoma (aHCC): results from CheckMate 040. J Clin Oncol 2020;38(4_suppl): 478. 478.

Finn RS, et al. Phase ib study of lenvatinib plus pembrolizumab in patients with unresectable hepatocellular carcinoma. J Clin Oncol: Off J Am Soc Clin Oncol 2020; 38(26): 2960–70.

Kudo M. Combination immunotherapy with anti-VEGF/TKI for hepatocellular carcinoma: present and future perspective. Hepatobiliary Surg Nutr 2020;10(2): 241–5.

Dudek M, et al. Auto-aggressive CXCR6 CD8 T cells cause liver immune pathology in NASH. Nature 2021;592(7854): 444–9.

Kudo M. Lack of response to immunotherapy in non-alcoholic steatohepatitis related hepatocellular carcinoma. Hepatobiliary Surg Nutr 2021;10(4): 522–5.