Programmed death-1 and its ligands in immune responses of cancers
Publish place: 3rd INTERNATIONAL NASTARAN CANCER SYMPOSIUM
Publish Year: 1396
نوع سند: مقاله کنفرانسی
زبان: English
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NASTARANCANSER03_236
تاریخ نمایه سازی: 7 اسفند 1396
Abstract:
Programmed Death-1 (PD-1) is a type 1 transmembrane protein of immunoglobulin (Ig) superfamily. Along with its ligands (PD-L1 and PD-L2), it is a crucial checkpoint in the regulation of immuneresponses. PD-L1 is expressed in both tumor cells and tumor-infiltrating immune cells in tumor microenvironment and becomes elevated in response to inflammation. In addition, in the central nervous system, PD-L1 is expressed in inflammatory cells as well as vascular endothelial cells and astrocytes. However, inflammation increases the number of tumor-infiltrating lymphocytes and macrophages and enhances tumor growth, but inflammation prevents T-cell antitumor activity. On the other hand, the elevated expression of PD-L1 in tumor cells mediates tumor-induced T-cell exhaustion and subsequent immune suppression in inflammatory environments, which allows tumors to evade immune surveillance. In addition, treatment with pro-inflammatory cytokines such as tumor necrosis factor (TNFa), IL-6, IL-17 and interferons (type 1 and 2) are able to up-regulate PD-L1 in several cell lines including endothelial cells, epithelial cells, T and B cells as well as cancer cells. In breast cancer cells, inflammation induces macrophages to secrete inflammatory cytokines such as TNF-α that activate NF-κB signaling, allowing NF-kB to up-regulate COP9 signalosome 5 (CSN5) expression by binding to its promoter. CSN5 reduces PD-L1 ubiquitination and stabilizes it and promotes PD-L1 expression in response to inflammatory TNFα signaling. Successful therapeutic outcome directed against both anti-PD-L1 and anti-PD-1 antibodies in patients with advanced melanoma, non-small cell cancer and renal cell cancer, along with the notable role of this checkpoint pathway in the inflammatory tumor context, suggest that PD-L1/PD-1 blockade may provide an opportunity for therapeutic intervention based on the role of immune checkpoint pathways to treat cancers associated with inflammation
Keywords:
Breast Cancer , Cell and Cancer , Solid Tumors , Cancer Treatment and Management , Targeted Cancer Therapy
Authors
Arash Soltani
Department Of Medical Biochemistry, Faculty Of Medicine, Mashhad University Of Medical Sciences,Mashhad, Iran
Mostafa Karimi-Roshan
Department Of Medical Biochemistry, Faculty Of Medicine, Mashhad University Of Medical Sciences, Mashhad, Iran
Amirali Jahani Yazdi
Department Of Laboratory Sciences, Faculty Of Paramedicine, Mashhad University Of Medical Sciences, Mashhad, Iran
Seyed Isaac Hashemy
Surgical Oncology Research Center, Mashhad University Of Medical Sciences, Mashhad, Iran