CTLA4 and neoplasm: Furthermore, resistance to anti-PD-1 therapy in RT-refractory tumors has been characterized by significant elevations in expression of genes associated with T-cell exhaustion, increased levels of checkpoints including LAG-3, TIM3, and CTLA-4 on CD4+ T-cells, and decreased number of CD11c + tumor-associated macrophages (TAMs) [81].