Immunotherapy in hepatocellular carcinoma: Primed to make a difference?

Abstract

Page 1 of 27 CancerThis is the author manuscript accepted for publication and has undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version record. Please cite this article as doi:10.1002/cncr.29769.This article is protected by copyright. All rights reserved. Accepted ArticleABSTRACT Advanced hepatocellular carcinoma (HCC) carries a dismal prognosis and the current treatment is limited to sorafenib, an agent with modest benefit. Preclinical data indicate that several immunologic mechanisms are at play to promote HCC development and growth while impairing effective antitumor immune surveillance. Several novel approaches geared at manipulating the immune response to HCC have suggested a therapeutic benefit in early stage clinical trials, indicating a real potential to augment tumor-specific immunity and improve outcomes in this disease. Herein, we review the barriers to an effective immune response against HCC and contemporary clinical investigations that may be "primed"to alter the natural history of HCC.

Advances in cholangiocarcinoma research: report from the third Cholangiocarcinoma Foundation Annual Conference

“…Immune checkpoint blockade has translated into a significant overall survival advantage in comparison to established therapies in some metastatic solid tumors (28). A critical question is whether immune checkpoint blockade will lead to clinical benefit and improved survival in patients with cholangiocarcinoma.…”

Advanced Hepatocellular Cancer: the Current State of Future Research

“…Moving beyond the VEGF-driven pathways may well be the key to increase the median OS further than the so-called 10-month antiangiogenic ceiling observed in this patient population [107].With the ongoing efforts in drug development, promising signals are indeed beginning to emerge, most notably with the c-MET inhibitors and also in the arena of immunotherapeutics [108]. It is important also to acknowledge the molecular intratumoral heterogeneity of this disease, an issue not addressed in many of the older studies.…”

Gastrointestinale Tumoren. Welches Potenzial hat die Immun-Checkpoint-Blockade bei fortgeschrittenen GI-Tumoren?

“…Auch hier sind die Patienten dringend auf die Entwicklung von neuen Therapiemöglichkeiten angewiesen, da der Tumor häufig erst dann diagnostiziert wird, wenn sich ein kurativer Therapieanspruch nicht mehr umsetzen lässt [20]. Für die Rationale einer Immun-CheckpointBlockade beim Leberzellkarzinom könnte unter anderem der Nachweis von dysregulierten Immun-Checkpoint-Molekülen oder tumorinfiltrierenden Lymphozyten (TIL) sprechen [21]. Die PD-1-Checkpoint-Blockade mit Nivolumab wird derzeit in der Phase-III-Studie CheckMate -459 klinisch untersucht: Eingeschlossen sind erwachsene Patienten (≥ 18 Jahre) mit einem histologisch bestätigten fortgeschrittenen HCC, die sich entweder für eine chirurgische Resektion und/oder lokal therapeutische Maßnah-men nicht eignen oder die nach einer chirurgischen und/oder lokaltherapeutischen Intervention progredient geworden sind.…”