![]() NKG7 mRNA therapy also improved the antitumor activity of murine tumor antigen–specific CD8 + T cells in an in vivo model of adoptive cell therapy. Transfection of T cells with NKG7 mRNA was sufficient to improve the tumor-cell killing ability of human T cells isolated from nonresponders and increase their response to anti–PD-1 or anti–PD-L1 therapy in vitro. Functional assays revealed that reduced NKG7 expression altered cytolytic granule number, trafficking, and calcium release, resulting in decreased CD8 + T-cell–mediated killing of tumor cells. Single-cell RNA-sequencing analysis of peripheral CD8 + T cells from patients treated with anti–PD-1 therapy showed that cells from nonresponders exhibited decreased expression of the cytolytic granule-associated molecule natural killer cell granule protein-7 ( NKG7). ![]() By evaluating human CD8 + T cells from responders versus nonresponders to treatment with immune checkpoint inhibitors, we sought to identify key factors associated with effective CTL function. ![]() However, the T-cell intrinsic factors required for human CTLs to accomplish highly efficient antitumor cytotoxicity are not well defined. Cytotoxic CD8 + T cells (CTL) are a crucial component of the immune system notable for their ability to eliminate rapidly proliferating malignant cells. ![]()
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January 2023
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