Translational oncology · 2022
Exosomes in malignant pleural effusion from lung cancer patients impaired the cytotoxicity of double-negative T cells.
СтатьяНазвание и аннотация: Перевод пока не подготовлен
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Wu Jingjing, Zhu Ranran, Wang Zhengxia, Chen Xueqin, Xu Tingting, Liu Yanan, Song Meijuan, Jiang Jingxian, Ma Qiyun, Chen Zhongqi, Liu Yuan, Wang Xiaoyue, Zhang Mingshun, Huang Mao, Ji Ningfei
Аннотация
CD3+CD4-CD8- double-negative T (DNT) cells are new weapons in cancer immunotherapy. Here, we explored DNT cells in malignant pleural effusions (MPEs) from lung cancer patients. DNT cells, especially TCRαβ+CD56- DNT cells, were increased in MPE from lung cancer patients. DNT cells highly expressed PD-1, TRAIL, NKG2D and DNAM-1. In contrast, FasL was barely detected in DNT cells. Compared with non-MPE cells, MPE-derived DNT cells expressed much higher levels of PD-1 and TRAIL. DNT cells from healthy peripheral blood donors potentially killed lung cancers, which was decreased by MPE supernatant. Exosomes from MPE supernatant expressed PD-1 and CEACAM1 and impaired the cytotoxicity of DNT cells. Blocking PD-1 and TIM3 rescued the cytotoxicity of DNT cells treated with MPE-derived exosomes. Overall, we demonstrated that the frequency of DNT cells in MPE from lung cancer patients was increased and that MPE-derived exosomes impaired the cytotoxicity of DNT cells via the PD-1/PD-L1 and CEACAM1/TIM3 pathways.