DOWN REGULATION OF C-FLIPL ENHANCE PD-1 BLOCKADE EFFICACY IN B16 MELANOMA

Down Regulation of c-FLIPL Enhance PD-1 Blockade Efficacy in B16 Melanoma

Down Regulation of c-FLIPL Enhance PD-1 Blockade Efficacy in B16 Melanoma

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Immune checkpoint blockade of programmed cell death protein 1 (PD-1) had an impressive long-lasting effect in a portion of advanced-stage melanoma patients, however, this therapy failed to induce responses in several patients; how to increase the objective response rate is very important.Cellular FLICE-inhibitory protein (c-FLIP) could inhibit apoptosis directly at the death-inducing signaling complex of death receptors and is also considered to be the main cause of immune escape.The overexpression of c-FLIPL occurs frequently in melanoma and its expression is associated ECHINAFORCE with the prognosis.We found that the level of c-FLIPL expression was associated with the PD-1 blockade response rate in melanoma patients.

Thus, we performed this research to investigate how c-FLIPL regulates immunotherapy in melanoma.We demonstrate that down regulation of c-FLIPL enhances the PD-1 blockade efficacy in B16 melanoma tumor model.Down regulation of c-FLIPL could increase the tumor apoptosis and enhance the antitumor response of T cells in the lymphocyte tumor cells co-culture system.Moreover, knockdown of c-FLIPL could Baby decrease the expression of PD-L1 and recruit more effector T cells in the tumor microenvironment.

Our results may provide a new combined therapeutic target for further improving the efficacy of PD-1 blockade in melanoma.

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