Mechanisms of Primary and Acquired Resistance to Immune Checkpoint Inhibitors in Patients with Hepatocellular Carcinoma

被引：33

作者：

De Lorenzo, Stefania ^{[1
]}

Tovoli, Francesco ^{[2
,3
]}

Trevisani, Franco ^{[2
,4
]}

机构：

[1] Azienda USL Bologna, Oncol Unit, I-40124 Bologna, Italy

[2] Univ Bologna, Dept Med & Surg Sci, I-40126 Bologna, Italy

[3] IRCCS Azienda Osped Univ Bologna, Div Internal Med Hepatobiliary & Immunoallerg Dis, I-40138 Bologna, Italy

[4] IRCCS Azienda Osped Univ Bologna, Unit Semeiot Liver & Alcohol Related Dis, I-40138 Bologna, Italy

来源：

CANCERS | 2022年 / 14卷 / 19期

关键词：

liver cancer; hepatocellular carcinoma; immunotherapy; immune checkpoint inhibitors; atezolizumab; bevacizumab; tremelimumab; durvalumab; tumour microenvironment; resistance; cirrhosis; outcome; GROWTH-FACTOR-BETA; DEATH-LIGAND; PD-1; BLOCKADE; MESENCHYMAL TRANSITION; TUMOR MICROENVIRONMENT; LIVER-CANCER; IMMUNOTHERAPY; EXPRESSION; IDENTIFICATION; NEOANTIGENS;

D O I：

10.3390/cancers14194616

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Simple Summary Immune checkpoint inhibitors (ICIs) are now a cornerstone of systemic treatment for hepatocellular carcinoma (HCC). However, their efficacy is blunted by mechanisms of tumour resistance in many patients. This review reports on the state of the art of resistance to ICIs, focusing on HCC, with the aim to provide clear and direct information to clinicians and researchers. Growing knowledge on the mechanisms of resistance to immunotherapy can indeed guide the choice of and expand the application of novel combined treatments. Hepatocellular carcinoma (HCC) is the most common liver cancer and a relevant global health problem. Immune checkpoint inhibitors (ICIs) represent the most effective systemic treatment for HCC. However, due to primary resistance, approximately 40% of HCC patients do not achieve a disease control with ICIs. Moreover, a similar proportion will experience disease progression after an initial response caused by secondary resistance. This review describes the mechanisms of primary and secondary resistance and reports the ongoing therapeutic strategies to overcome these obstacles.

引用

页数：16

共 94 条

[1] Use of Immune Checkpoint Inhibitors in the Treatment of Patients With Cancer and Preexisting Autoimmune Disease A Systematic Review [J].

Abdel-Wahab, Noha ;

Shah, Mohsin ;

Lopez-Olivo, Maria A. ;

Suarez-Almazor, Maria E. .

ANNALS OF INTERNAL MEDICINE, 2018, 168 (02) :121-+

[2]

Abou-Alfa Ghassan K, 2022, NEJM Evid, V1, pEVIDoa2100070, DOI 10.1056/EVIDoa2100070

[3] Cirrhosis-associated immune dysfunction: Distinctive features and clinical relevance [J].

Albillos, Agustin ;

Lario, Margaret ;

Alvarez-Mon, Melchor .

JOURNAL OF HEPATOLOGY, 2014, 61 (06) :1385-1396

[4] NAD-Biosynthetic and Consuming Enzymes as Central Players of Metabolic Regulation of Innate and Adaptive Immune Responses in Cancer [J].

Audrito, Valentina ;

Manago, Antonella ;

Gaudino, Federica ;

Sorci, Leonardo ;

Messana, Vincenzo Gianluca ;

Raffaelli, Nadia ;

Deaglio, Silvia .

FRONTIERS IN IMMUNOLOGY, 2019, 10

[5] Tumor Interferon Signaling Regulates a Multigenic Resistance Program to Immune Checkpoint Blockade [J].

Benci, Joseph L. ;

Xu, Bihui ;

Qiu, Yu ;

Wu, Tony J. ;

Dada, Hannah ;

Twyman-Saint Victor, Christina ;

Cucolo, Lisa ;

Lee, David S. M. ;

Pauken, Kristen E. ;

Huang, Alexander C. ;

Gangadhar, Tara C. ;

Amaravadi, Ravi K. ;

Schuchter, Lynn M. ;

Feldman, Michael D. ;

Ishwaran, Hemant ;

Vonderheide, Robert H. ;

Maity, Amit ;

Wherry, E. John ;

Minn, Andy J. .

CELL, 2016, 167 (06) :1540-+

[6] Coregulation of CD8+ T cell exhaustion by multiple inhibitory receptors during chronic viral infection [J].

Blackburn, Shawn D. ;

Shin, Haina ;

Haining, W. Nicholas ;

Zou, Tao ;

Workman, Creg J. ;

Polley, Antonio ;

Betts, Michael R. ;

Freeman, Gordon J. ;

Vignali, Dario A. A. ;

Wherry, E. John .

NATURE IMMUNOLOGY, 2009, 10 (01) :29-37

[7] Mechanisms of disease:: Role of transforming growth factor β in human disease. [J].

Blobe, GC ;

Schiemann, WP ;

Lodish, HF .

NEW ENGLAND JOURNAL OF MEDICINE, 2000, 342 (18) :1350-1358

[8] Endpoints in clinical trials for liver cancer and their value in evidence-based clinical decision making: An unresolved Gordian knot [J].

Bruix, Jordi .

JOURNAL OF HEPATOLOGY, 2021, 74 (06) :1483-1488

[9] GNS561, a clinical-stage PPT1 inhibitor, is efficient against hepatocellular carcinoma via modulation of lysosomal functions [J].

Brun, Sonia ;

Bestion, Eloine ;

Raymond, Eric ;

Bassissi, Firas ;

Jilkova, Zuzana Macek ;

Mezouar, Soraya ;

Rachid, Madani ;

Novello, Marie ;

Tracz, Jennifer ;

Hamai, Ahmed ;

Lalmanach, Gilles ;

Vanderlynden, Lise ;

Legouffe, Raphael ;

Stauber, Jonathan ;

Schubert, Thomas ;

Plach, Maximilian G. ;

Courcambeck, Jerome ;

Drouot, Cyrille ;

Jacquemot, Guillaume ;

Serdjebi, Cindy ;

Roth, Gael ;

Baudoin, Jean-Pierre ;

Ansaldi, Christelle ;

Decaens, Thomas ;

Halfon, Philippe .

AUTOPHAGY, 2022, 18 (03) :678-694

[10] Programmed Death Ligand 1 Expression in Hepatocellular Carcinoma: Relationship With Clinical and Pathological Features [J].

Calderaro, Julien ;

Rousseau, Benoit ;

Amaddeo, Giuliana ;

Mercey, Marion ;

Charpy, Cecile ;

Costentin, Charlotte ;

Luciani, Alain ;

Zafrani, Elie-Serge ;

Laurent, Alexis ;

Azoulay, Daniel ;

Lafdil, Fouad ;

Pawlotsky, Jean-Michel .

HEPATOLOGY, 2016, 64 (06) :2038-2046

← 1 2 3 4 5 6 7 8 9 10 →