Journal
TRANSLATIONAL ONCOLOGY
Volume 27, Issue -, Pages -Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.tranon.2022.101564
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CD3(+)CD4(-)CD8(-) double-negative T (DNT) cells are increased in malignant pleural effusions (MPEs) from lung cancer patients. These DNT cells express high levels of PD-1 and TRAIL, and their cytotoxicity is impaired by exosomes derived from MPEs.
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 TCR alpha beta(+)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.
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