Immune checkpoint blockade opens a new way to cancer immunotherapy

Abstract

Among the main promising systems to triggering therapeutic antitumor immunity is the blockade of immune checkpoints. Immune checkpoint pathways regulate the control and eradication of infections, malignancies, and resistance against a host of autoantigens. Initiation point of the immune response is T cells, which have a critical role in this pathway. As several immune checkpoints are initiated by ligand–receptor interactions, they can be freely blocked by antibodies or modulated by recombinant forms of ligands or receptors. Antibodies against cytotoxic T‐lymphocyte‐associated antigen 4 (CTLA‐4) were the first immunotherapeutics that achieved the US Food and Drug Administration approval. Preliminary clinical results with the blockers of additional immune checkpoint proteins, such as programmed cell death protein 1 (PD‐1) indicate extensive and different chances to boost antitumor immunity with the objective of conferring permanent clinical effects. This study provides an overview of the immune checkpoint pathways, including CTLA‐4, PD‐1, lymphocyte activation gene 3, T‐cell immunoglobulin and mucin domain 3, B7‐H3, and diacylglycerol kinase α and implications of their inhibition in the cancer therapy.

A Tumor-Specific Super-Enhancer Drives Immune Evasion by Guiding Synchronous Expression of PD-L1 and PD-L2

“…T cell-negative regulation primarily relies on many inhibitory checkpoint molecules that are expressed in different stages of T cells. CTLA-4 (cytotoxic T-lymphocyteassociated protein 4) and PD-1 (programmed cell death protein 1) are the two most studied inhibitory checkpoint molecules, and their blocking antibodies, such as ipilimumab, pembrolizumab, and nivolumab, have been approved for clinical treatment in multiple types of tumors (Sadreddini et al, 2019). In various types of advanced cancers, immune checkpoint blockade has been demonstrated to have groundbreaking improvements in clinical response compared to standard therapies.…”

Curcumin and Photobiomodulation in Chronic Viral Hepatitis and Hepatocellular Carcinoma

“…At the initiation of the tumor process, naïve T cells have a special role because they are becoming operative, set into motion the microenvironment of the tumor formation, and fight to remove immunogenic neoplastic cells [ 161 ].…”

Subcellular Localization Relevance and Cancer-Associated Mechanisms of Diacylglycerol Kinases

“…Recently, exploring immune-based therapeutic systems, such as blockage of immune checkpoints or adoptive cell transfer (ACT) that stimulate antitumor immunity by targeting and attacking tumor cells, seems promising because of its specificity. The starting point of this immune response is represented by chimeric antigen receptor (CAR)-T cells [120]. Interestingly, incoming reports suggest that targeting DGK activity could be a strong approach to reinforce the anti-tumor functions of T cells [7].…”