{Reference Type}: Journal Article
{Title}: Enhanced T cell immune activity mediated by Drp1 promotes the efficacy of PD-1 inhibitors in treating lung cancer.
{Author}: Ma J;Song J;Yi X;Zhang S;Sun L;Huang L;Han C;
{Journal}: Cancer Immunol Immunother
{Volume}: 73
{Issue}: 2
{Year}: 2024 Feb 10
{Factor}: 6.63
{DOI}: 10.1007/s00262-023-03582-5
{Abstract}: <B>BACKGROUND: </B>Dynamin-related protein 1 (Drp1)-mediated mitochondrial fission plays important roles in the activation, proliferation, and migration of T cells.<BR><B>METHODS: </B>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.<BR><B>RESULTS: </B>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.<BR><B>CONCLUSIONS: </B>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.