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Role of Programmed Death‐Ligand 1 in Cancer
Author(s) -
Link Tina,
Dilip Megha,
Caruso Olivia,
Chang Margaret,
Kona Abhinav,
Liu Jesse,
Nathan Ajay,
Singh Anita,
ThomasWilkinson Shiloh
Publication year - 2019
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2019.33.1_supplement.647.19
Subject(s) - cytotoxic t cell , immune system , cancer cell , programmed cell death , cd8 , pd l1 , immune checkpoint , cancer research , t cell , ligand (biochemistry) , chemistry , microbiology and biotechnology , cancer , receptor , immunotherapy , biology , immunology , apoptosis , biochemistry , genetics , in vitro
Programmed death‐1 (PD‐1) is an immunoregulatory receptor on cytotoxic T cells that suppresses the immune system upon interaction with its two ligands, programmed death ligand‐1 (PD‐L1) and programmed death ligand‐2 (PD‐L2). Programmed death‐ligand 1 (PD‐L1), previously known as “CD279”, is made up of 268 amino acids with a crystal structure. It is part of the immunoglobulin superfamily with a transmembrane domain and a tail which contains two phosphorylation sites. PD‐L1 is located on the cell surface of monocytes, B cells, T cells, and dendritic cells, and works in conjunction with PD‐1 to modulate an immune response. In binding with its ligand PD‐1 on an activated T cell, PD‐L1 suppresses the immune response of the T cell, rendering it inactive. PD‐L1's other ligand, the PD‐L2, also plays a role in deregulating the T cell immune response. Many cancer cells express PD‐L1, attenuating immunity and allowing cancer cell proliferation. This distorted relationship provides a focal point for cancer research. Attempts to inhibit the effects of PD‐L1 are concentrated on blocking its interaction to PD‐1, resurrecting the immune response, and thereby allowing CD8+ cytotoxic cells to attack tumor cells. Potential treatments include the development of an anti‐PD‐L1 antibody therapy to induce tumor remissions for patients with different types and stages of cancer. Supporting promising PD‐L1 research, the FDA has approved the PD‐L1 biomarker to accelerate investigation into a potential cure for cancer. In 2018, James P. Allison and Tasuku Hojo received the Nobel Prize in Medicine for research on PD‐L1 that lead to the discovery of checkpoint inhibitors that release immune responses, thereby reactivating T‐cells. The Walton High School MSOE Center for Biomolecular Modeling SMART Team has designed a 3‐D model of PD‐1 in interaction with its ligand PDL‐1 using JMOL to investigate the relationship between the structure and function of the proteins in relation to its current role in cancer development and its future in potential treatment. This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .