220P HDAC1 inhibition sensitizes refractory tumor cells to anti-PD-1 therapy by upregulation chemokine expression and stimulating T cells infiltration into tumor beds

Immune checkpoint inhibitors (ICIs), exemplified by anti-PD-1 are promising treatments for many tumors. However, the majority of patients lack effective responses because emergence immune-refractory tumors that disrupt amplification antitumor immunity. In cases, one major causes resistance to these agents is limited tumor penetrance effector T cells. Durable clinical using anti–PD-1 have been associated with cell–inflamed microenvironment (TME) favoring infiltration functional cytotoxic lymphocytes (CTLs). Efforts identify therapeutic approaches able turn immune cold hot enhancing cell into bed currently undertaken. We analyzed transcriptomic data on cancer treated anti-PD-1and newly established preclinical mouse models refractory anti-PD-1. The effect genetic ablation or pharmacological inhibition HDAC1 were approached transwell migration assay, Immunostaining, flow cytometry and RT-qPCR. confirmed enhanced against when combining inhibitor in models. a key factor insufficient CTL-mediated killing Ablation significantly upregulates expression CXCL10 MCL-1 cells, enforcing apoptosis models, substantially smaller size burden mice both compared those either agent alone. overall numbers CD8 cells tumor-reactive expressing granzyme B higher combination treatment group than other groups. Preliminary suggest switched phenotypes from an immune-stimulatory feature simultaneously reversing NANOG-mediated states, thereby overcoming PD-1 blockade.