期刊
BIOMEDICINES
卷 10, 期 6, 页码 -出版社
MDPI
DOI: 10.3390/biomedicines10061450
关键词
Lewis lung carcinoma; reprogramming; MEK inhibitors; cancer immunotherapy
资金
- Ministry of Science and Higher Education Russian Federation [075-15-2020-773]
CD8(+) T-lymphocytes play a crucial role in the immune response against lung cancer. Reprogrammed T-lymphocytes, using MEK inhibitors and PD-1 blockers, show increased antitumor activity. This reprogramming approach demonstrates significant antitumor effects both in vitro and in vivo.
CD8(+) T-lymphocytes play a key role in antitumor immune response. Patients with lung cancer often suffer from T-lymphocyte dysfunction and low T-cell counts. The exhaustion of effector T-lymphocytes largely limits the effectiveness of therapy. In this study, reprogrammed T-lymphocytes used MEK inhibitors and PD-1 blockers to increase their antitumor activity. Antitumor effects of reprogrammed T-lymphocytes were shown in vitro and in vivo in the Lewis lung carcinoma model. The population of T- lymphocytes with persistent expression of CCR7 was formed as a result of reprogramming. Reprogrammed T-lymphocytes were resistant to apoptosis and characterized by high cytotoxicity against Lewis lung carcinoma (LLC) cells in vitro. Administration of reprogrammed T-lymphocytes to C57BL/6 mice with LLC reduced the number of lung metastases. The antitumor effect resulted from the elimination of tumor cells and cancer stem cells, and the effect of therapy on cytotoxic T-lymphocyte counts. Thus, reprogramming of T-lymphocytes using MEK inhibitors is a promising approach for targeted therapy of lung cancer.
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