%0 Journal Article
%T Enhanced T cell immune activity mediated by Drp1 promotes the efficacy of PD-1 inhibitors in treating lung cancer.
%A Ma J
%A Song J
%A Yi X
%A Zhang S
%A Sun L
%A Huang L
%A Han C
%J Cancer Immunol Immunother
%V 73
%N 2
%D 2024 Feb 10
%M 38340166
%F 6.63
%R 10.1007/s00262-023-03582-5
%X BACKGROUND: Dynamin-related protein 1 (Drp1)-mediated mitochondrial fission plays important roles in the activation, proliferation, and migration of T cells.
METHODS: We investigated the synergistic effect of Drp1-mediated T cell antitumor activities and programmed cell death protein 1 (PD-1) blockade for treating lung cancer through in vitro co-culture experiments and an in vivo nude mouse xenograft model.
RESULTS: High expression levels of Drp1 positively regulated T cell activation, enhanced T cell-induced suppression of lung cancer cells, promoted CD8+ T cell infiltration in the tumor and spleen, and significantly enhanced the antitumor immune response of the PD-1 inhibitor pembrolizumab. The mechanism of this synergistic antitumor effect involved the secretion of immune killing-related cytokines and the regulation of the PD-1-ERK/Drp1 pathway in T cells.
CONCLUSIONS: Our findings suggest that modifying Drp1 expression in T cells could serve as a potential therapeutic target for enhancing the antitumor immune response in future immunotherapies.