PD-L1 Overexpression, SWI/SNF Complex Deregulation, and Profound Transcriptomic Changes Characterize Cancer-Dependent Exhaustion of Persistently Activated CD4+ T Cells

Growing tumors avoid recognition and destruction by the immune system. During continuous stimulation of tumor-infiltrating lymphocytes (TILs) tumors, TILs become functionally exhausted; thus, they unable to kill tumor cells produce certain cytokines lose their ability proliferate. This collectively results in escape cancer cells. Here, we show that breast expressing PD-L1 can accelerate exhaustion persistently activated human effector CD4+ T cells, manifesting high PD-1 expression level son cell surfaces, decreased glucose metabolism genes, strong downregulation SWI/SNF chromatin remodeling complex subunits, p21 cycle inhibitor upregulation. inhibition proliferation reduction numbers. The RNAseq analysis on exhausted indicated overexpression IDO1 genes encoding pro-inflammatory chemokines. Some interleukins were also detected media from co-cultured with was observed after co-cultivation other lines overexpressing PD-L1, which suggested existence a general mechanism induced ChIP promoter region BRM recruitment control replaced BRG1 EZH2 strongly These findings suggest epi-drugs such as inhibitors may be used immunomodulators treatment.