Vascular Normalization Augments the Anti-tumor Efficacy of Combined HDAC Inhibitor with PD-1 Therapy in Solid Tumors (PRJCA027883)

Immunotherapy has made remarkable strides in cancer treatment; however, its efficacy remains limited in various solid tumors when used as a monotherapy. Epigenetic regulation and vascular abnormalization play pivotal roles in tumor development. Exploring potential new drug combinations to further enhance immunotherapy efficacy in solid tumors are urgent issues that need to be addressed. Here, we demonstrated that the HDAC inhibitor, chidamide, not only enhanced chromatin accessibility at the promoters of effector molecules in CD8+ T cells, thereby augmenting their anti-tumor capabilities, but also induced the expression of VEGFa in pro-tumorigenic macrophages, compromising their synergistic effect with immunotherapy by reducing infiltration of immune cells. Remarkably, combining anti-angiogenesis therapy counteracted the angiogenesis effects of HDAC inhibitor on macrophages, significantly enhancing the infiltration and functionality of cytotoxic CD8+ T cells. These findings highlighted the potential synergistic application of HDAC inhibitors, anti-angiogenesis therapy, and immunotherapy across diverse solid tumors.