Research Progress on the Mechanism and Clinical Data of Cereblon in Reversing the Resistance of Lung Cancer to PD-1 Antibody by T cells / 中国肺癌杂志

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.
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Lichen Planus Developed During the Treatment with Nivolumab in a Patient with Lung Cancer: A Case Report and Literature Review / 대한피부과학회지

Nivolumab is a fully-humanized IgG4 monoclonal antibody that competitively binds to the programmed cell death receptor-1 protein (an immune check-point molecule) present on activated T cells. Nivolumab is approved for the treatment of advanced melanoma, lung cancer, and renal cell carcinoma. It attenuates the inactivation of cytotoxic CD8+ T cells and, produces an antitumor effect; however it may be associated with immune-related adverse events, including the development of lichen planus (LP). A 72-year-old man presented with a 2-month history of multiple, polygonal, purplish papules on the dorsal aspect of both hands. He was diagnosed with large cell neuroendocrine carcinoma (LCNEC) of the lung 4 years earlier and was treated with nivolumab (3 mg/kg every 2 weeks) for 9 months. By the 14th course of nivolumab therapy, the patient developed multiple rashes on the dorsal aspect of both hands, and biopsy was consistent with findings of LP. We report a rare case of LP in a patient with lung cancer treated with nivolumab.