PD-1/PD-L1 checkpoint inhibitors in advanced hepatocellular carcinoma immunotherapy

Abstract

Hepatocellular carcinoma (HCC) has a high prevalence and mortality rate worldwide. Sorafenib monotherapy has been the standard of first-line treatment for advanced HCC for a long time, but there are still many shortcomings. In recent years, with the deepening of research on tumor immune microenvironment, researchers have begun to explore new approaches in immunotherapy, and the introduction of immune checkpoint inhibitors has brought fundamental changes to the treatment of HCC. Programmed cell death protein 1 (PD-1) is an immune checkpoint molecule that plays an important role in down-regulating immune system function and promoting tolerance. Programmed cell death ligand 1 (PDL-1) is involved in tumor immune evasion by binding to PD-1, resulting in failure of treatment. Currently, immunotherapy targeting the PD-1/PD-L1 axis has achieved unprecedented success in HCC, but it also faces great challenges, with its low remission rate still to be solved. For most patients with HCC, the PD-1/PD-L1 pathway is not the only rate limiting factor of antitumor immunity, and blocking only the PD-1/PD-L1 axis is not enough to stimulate an effective antitumor immune response; thus, combination therapy may be a better option. In this study, changes in the immune microenvironment of HCC patients were reviewed to clarify the feasibility of anti-PD-1/PD-L1 therapy, and a series of monotherapy and combination therapy clinical trials were summarized to verify the safety and efficacy of this newly developed treatment in patients with advanced HCC. Furthermore, we focused on hyperprogressive disease and drug resistance to gain a better understanding of PD-1/PD-L1 blockade as a promising treatment.

Drug‐Eluting Shear‐Thinning Hydrogel for the Delivery of Chemo‐ and Immunotherapeutic Agents for the Treatment of Hepatocellular Carcinoma

“…High PD‐L1 expression can impair effector T cell performance and hasten their depletion, preventing them from efficiently identifying and killing cancer cells. [ 57 ] The high expression of PD‐L1 in liver cancer also offers a chance for immunotherapy, specifically immune checkpoint blocking therapy, making this type of cancer prone to ICIs, specifically aPD‐1 or aPD‐L1 antibodies. Immunotherapies that target the PD‐1/PD‐L1 pathway can interfere with the PD‐1/PD‐L1 interaction and restore the antitumor immune response.…”

The Regulatory Axis of PD-L1 Isoform 2/TNF/T Cell Proliferation Is Required for the Canonical Immune-Suppressive Effects of PD-L1 Isoform 1 in Liver Cancer

“…This combination therapy regimen was well tolerated, and the toxicity was easily controlled [ 32 ]. Recently, a Himalaya phase III study demonstrated that both durvalumab combined with tremelimumab (anti-CTLA-4) and durvalumab monotherapy significantly improved the survival of HCC patients [ 33 ]. However, several challenges have yet to be addressed, such as the low remission rate and the lack of applicable standards.…”

Association of hepatitis B virus infection with head and neck cancer: a propensity-matched study

“…After the up-regulation of PD-1, HBV-speci c CD8 + T lymphocytes are in a highly depleted and hypofunctional state. Therefore, PD-1/PD-L1 immune checkpoint inhibitors (ICIs) become a new approach to treat hepatocellular carcinoma [32,33]. As we all know, immune escape exerts a critical effect on HNC occurrence and development, thus immunotherapy is a good choice.…”