Gastroenterology, Год журнала: 2022, Номер 164(1), С. 72 - 88.e18
Опубликована: Сен. 12, 2022
Язык: Английский
Nature Reviews Clinical Oncology, Год журнала: 2021, Номер 19(3), С. 151 - 172
Опубликована: Ноя. 11, 2021
Язык: Английский
Процитировано
1170
Nature, Год журнала: 2021, Номер 592(7854), С. 450 - 456
Опубликована: Март 24, 2021
Abstract Hepatocellular carcinoma (HCC) can have viral or non-viral causes 1–5 . Non-alcoholic steatohepatitis (NASH) is an important driver of HCC. Immunotherapy has been approved for treating HCC, but biomarker-based stratification patients optimal response to therapy unmet need 6,7 Here we report the progressive accumulation exhausted, unconventionally activated CD8 + PD1 T cells in NASH-affected livers. In preclinical models NASH-induced therapeutic immunotherapy targeted at programmed death-1 (PD1) expanded within tumours did not lead tumour regression, which indicates that immune surveillance was impaired. When given prophylactically, anti-PD1 treatment led increase incidence NASH–HCC and number size nodules, correlated with increased hepatic CXCR6 , TOX TNF cells. The HCC triggered by prevented depletion neutralization, suggesting help induce NASH–HCC, rather than invigorating executing surveillance. We found similar phenotypic functional profiles from humans NAFLD NASH. A meta-analysis three randomized phase III clinical trials tested inhibitors PDL1 (programmed death-ligand 1) more 1,600 advanced revealed improve survival two additional cohorts, NASH-driven who received anti-PDL1 showed reduced overall compared other aetiologies. Collectively, these data show particularly might be less responsive immunotherapy, probably owing NASH-related aberrant cell activation causing tissue damage leads impaired Our provide a rationale according underlying aetiology studies as primary adjuvant treatment.
Язык: Английский
Процитировано
938
Nature Reviews Gastroenterology & Hepatology, Год журнала: 2021, Номер 18(8), С. 525 - 543
Опубликована: Апрель 13, 2021
Hepatocellular carcinoma (HCC) is a prevalent disease with progression that modulated by the immune system. Systemic therapy used in advanced stage and until 2017 consisted only of antiangiogenic tyrosine kinase inhibitors (TKIs). Immunotherapy checkpoint has shown strong anti-tumour activity subset patients combination anti-PDL1 antibody atezolizumab VEGF-neutralizing bevacizumab or will soon become standard care as first-line for HCC, whereas anti-PD1 agents nivolumab pembrolizumab are after TKIs several regions. Other strategies such adoptive T-cell transfer, vaccination virotherapy have not yet demonstrated consistent clinical activity. Major unmet challenges HCC immunotherapy discovery validation predictive biomarkers, advancing treatment to earlier stages disease, applying liver dysfunction more effective combinatorial sequential approaches. Combinations other systemic local treatments perceived most promising opportunities some already under evaluation large-scale trials. This Review provides up-to-date information on best use currently available immunotherapies therapeutic development. Immunotherapeutic interventions might be tools hepatocellular carcinoma. carcinoma, mechanisms response resistance,
Язык: Английский
Процитировано
938
The Lancet Oncology, Год журнала: 2021, Номер 23(1), С. 77 - 90
Опубликована: Дек. 13, 2021
Язык: Английский
Процитировано
840
Hepatology, Год журнала: 2023, Номер 78(6), С. 1922 - 1965
Опубликована: Май 18, 2023
Singal, Amit G.; Llovet, Josep M.; Yarchoan, Mark; Mehta, Neil; Heimbach, Julie K.; Dawson, Laura A.; Jou, Janice H.; Kulik, Agopian, Vatche Marrero, Jorge Mendiratta-Lala, Mishal; Brown, Daniel B.; Rilling, William S.; Goyal, Lipika; Wei, Alice C.; Taddei, Tamar H. Author Information
Язык: Английский
Процитировано
713
Nature Reviews Gastroenterology & Hepatology, Год журнала: 2022, Номер 20(4), С. 203 - 222
Опубликована: Ноя. 11, 2022
Язык: Английский
Процитировано
442
Nature Medicine, Год журнала: 2022, Номер 28(8), С. 1599 - 1611
Опубликована: Июнь 23, 2022
Язык: Английский
Процитировано
363
Nature Reviews Clinical Oncology, Год журнала: 2023, Номер 20(12), С. 864 - 884
Опубликована: Окт. 26, 2023
Язык: Английский
Процитировано
324
Nature Cancer, Год журнала: 2022, Номер 3(4), С. 386 - 401
Опубликована: Апрель 28, 2022
Язык: Английский
Процитировано
286
JAMA Oncology, Год журнала: 2020, Номер 7(1), С. 113 - 113
Опубликована: Окт. 22, 2020
For more than a decade, sorafenib has been the only systemic treatment option for patients with advanced hepatocellular carcinoma (HCC). However, rapid progress over past few years led to approval of other angiogenesis inhibitors and several immune checkpoint blockers (ICBs) that have added armamentarium HCC. Moreover, recent success combination bevacizumab atezolizumab signals an important change in front-line HCC.This review summarizes rapidly emerging clinical data on promise challenges implementing ICBs HCC discusses unmet need biomarkers predict response or resistance therapy. Two strategies target immunosuppression tumors are also discussed: one proven (vascular endothelial growth factor pathway inhibition) currently under investigation (transforming factor-β inhibition). The rationale preliminary evidence how their inhibition may reprogram immunosuppressive milieu enhance efficacy reviewed.The successes failures ICBs, alone combination, provided insights into implement this novel therapy new avenues immunotherapy disease.
Язык: Английский
Процитировано
266