Research Progress on the Mechanism and Clinical Data of Cereblon
in Reversing the Resistance of Lung Cancer to PD-1 Antibody by T cells.
10.3779/j.issn.1009-3419.2020.102.49
- Author:
Jingjing GUO
1
;
Di MU
1
;
Ying HAN
1
Author Information
1. National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Key Laboratory of Cancer Immunology and Biotherapy, Tianjin Medicial University Cancer Institute and Hospital, Tianjin 300060, China.
- Publication Type:Journal Article
- Keywords:
Cereblon;
Lung neoplasms;
Programmed cell death receptor 1 antibody;
T cell
- From:
Chinese Journal of Lung Cancer
2021;24(1):49-55
- CountryChina
- Language:Chinese
-
Abstract:
Programmed cell death receptor 1 (PD-1) is a membrance-spanning protein mostly expressed in the T cell, and combines with programmed cell death ligand 1 (PD-L1) in the targeting cell. When binding to the ligand on tumor cells, PD-1 as an immunosuppressive molecule, can inhibit the immune function of T cells, thus tumor immune escape. For example, depletion of peripheral effector T cell and accelerate the transformation of effector T cells into regulator T cells. To solve this problem, PD-1 antibody is used to bind to PD-1 on T cells to inhibit the interaction between PD-1 on the T cells and PD-L1 on the tumor cells so that it can restore the function of T cells to kill tumor cell. PD-1 antibodies, such as Nivolumab and Pembrolizumb, are approved as a first-line treatment for advanced non-small cell lung cell cancer. However, due to the interaction of tumor cells, T cells and cytokines, some patients developed drug resistance which reduces the efficacy of immunotherapy. Hence, how to overcome resistance has become a urgent problem. Cereblon (CRBN), a substrate receptor of the DDB1-cullin-RING E3 ubiquitin ligase complex and the only known molecular receptor of immunoregulatory drugs, has been found to reverse PD-1 antibody resistance by binding to CRBN regulatory agents (CMS), exert T cell immune function by regulating proliferation, activation and metabolism of T cell. In this paper, the mechanism of down-regulation of T cells leading to resistance of PD-1 antibody in lung cancer, the mechanism of CRBN regulating T cells, and research progress of CRBN regulator in the treatment of lung cancer were reviewed.
.
