Journal article
Specific CD8+ T cell response immunotherapy for hepatocellular carcinoma and viral hepatitis
- Abstract:
- Hepatocellular carcinoma (HCC), chronic hepatitis B (CHB) and chronic hepatitis C (CHC) are characterized by exhaustion of the specific CD8+ T cell response. This process involves enhancement of negative co-stimulatory molecules, such as programmed cell death protein-1 (PD-1), cytotoxic T-lymphocyte antigen-4 (CTLA-4), 2B4, Tim-3, CD160 and LAG-3, which is linked to intrahepatic overexpression of some of the cognate ligands, such as PD-L1, on antigen presenting cells and thereby favouring a tolerogenic environment. Therapies that disrupt these negative signalling mechanisms represent promising therapeutic tools with the potential to restore reactivity of the specific CD8+ T cell response. In this review we discuss the impressive in vitro and in vivo results that have been recently achieved in HCC, CHB and CHC by blocking these negative receptors with monoclonal antibodies against these immune checkpoint modulators. The article mainly focuses on the role of CTLA-4 and PD-1 blocking monoclonal antibodies, the first ones to have reached clinical practice. The humanized monoclonal antibodies against CTLA-4 (tremelimumab and ipilimumab) and PD-1 (nivolumab and pembrolizumab) have yielded good results in testing of HCC and chronic viral hepatitis patients. Trelimumab, in particular, has shown a significant increase in the time to progression in HCC, while nivolumab has shown a remarkable effect on hepatitis C viral load reduction. The research on the role of ipilimumab, nivolumab and pembrolizumab on HCC is currently underway.
- Publication status:
- Published
- Peer review status:
- Peer reviewed
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(Preview, Version of record, pdf, 1.4MB, Terms of use)
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- Publisher copy:
- 10.3748/wjg.v22.i28.6469
Authors
+ Instituto de Salud Carlos III
More from this funder
- Grant:
- “Gilead Spain & Instituto de Salud Carlos III”, No. GLD14_00217
- Publisher:
- Baishideng Publishing Group
- Journal:
- World Journal of Gastroenterology More from this journal
- Volume:
- 22
- Issue:
- 28
- Pages:
- 6469-6483
- Publication date:
- 2016-07-28
- Acceptance date:
- 2016-06-15
- DOI:
- EISSN:
-
2219-2840
- ISSN:
-
1007-9327
- Pmid:
-
27605882
- Language:
-
English
- Keywords:
- Pubs id:
-
pubs:836264
- UUID:
-
uuid:361efccd-1e74-4cbf-9a89-ca96e938995b
- Local pid:
-
pubs:836264
- Source identifiers:
-
836264
- Deposit date:
-
2018-04-23
Terms of use
- Copyright holder:
- Moreno-Cubero and Larrubia
- Copyright date:
- 2016
- Notes:
-
Copyright © 2016 The Authors. Published by Baishideng Publishing Group Inc. This article is an open-access article which was
selected by an in-house editor and fully peer-reviewed by external
reviewers. It is distributed in accordance with the Creative
Commons Attribution Non Commercial (CC BY-NC 4.0) license,
which permits others to distribute, remix, adapt, build upon this
work non-commercially, and license their derivative works on
different terms, provided the original work is properly cited and
the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
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