Immune checkpoints in targeted-immunotherapy of pancreatic cancer: New hope for clinical development

Abstract

Immunotherapy has been recently considered as a promising alternative for cancer treatment. Indeed, targeting of immune checkpoint (ICP) strategies have shown significant success in human malignancies. However, despite remarkable success of cancer immunotherapy in pancreatic cancer (PCa), many of the developed immunotherapy methods show poor therapeutic outcomes in PCa with no or few effective treatment options thus far. In this process, immunosuppression in the tumor microenvironment (TME) is found to be the main obstacle to the effectiveness of antitumor immune response induced by an immunotherapy method. In this paper, the latest findings on the ICPs, which mediate immunosuppression in the TME have been reviewed. In addition, different approaches for targeting ICPs in the TME of PCa have been discussed. This review has also synopsized the cutting-edge advances in the latest studies to clinical applications of ICP-targeted therapy in PCa.

YPD-30, a prodrug of YPD-29B, is an oral small-molecule inhibitor targeting PD-L1 for the treatment of human cancer

“…Anti-human cytotoxic T lymphocyte antigen 4 (CTLA4) antibody was the first immune checkpoint inhibitor to be officially approved by the U.S. Food and Drug Association (FDA), followed by anti-programmed death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) antibodies 3 . As the pronounced therapeutic effects of these immune checkpoint inhibitors have been repeatedly reported in different clinical trials, the indications of these immunotherapy drugs are now expanding to melanoma, skin cancer, bladder cancer, head and neck cancer, lung cancer, lymphoma, gastric cancer, pancreatic cancer 4 and urothelial carcinoma. Furthermore, anti-PD-1 antibody can also be used in the treatment of patients with unresectable or metastatic tumors with high microsatellite instability (MSI-H), or mismatch repair deficient tumors 5 , 6 .…”

Clinical Significance and Bioinformatics Analysis of SMC Family in Pancreatic Adenocarcinoma

“…The treatment of PAAD remains a considerable challenge to date. In addition to traditional surgical intervention, chemotherapy, radiotherapy, and other treatment modalities, immunotherapy has become the hope of PAAD therapy [33]. Tumor immunotherapy reshapes the tumor immune microenvironment and transforms tumor cells from "cold" to "hot" [34].…”

Exosomes as bio-inspired nanocarriers for RNA delivery: preparation and applications

“…Tumor cell-derived exosomes were documented to induce immunosuppression by stimulating regulatory T cells and immunosuppressive myeloid-derived suppressor cells, suppressing DC differentiation and NK cell cytotoxicity, and inducing T cell apoptosis [ 99 , 100 ]. While, exosomes that derived from tumor cells under stress condition could induce antitumor immune responses because they contain more HSPs (heat-shock proteins) in addition to tumor antigens.…”