CD28 and neoplasm: Moreover, immunosuppressive TME often contain exosomal PD-L1, immunosuppressive cells such as myeloid-derived suppressor cells, regulatory T cells, and tumor-associated macrophages which contribute to promote activation of coinhibitory receptors (e.g., PD-L1, CTLA-4, TIM3, TIGHT) and inhibition of costimulatory receptor (e.g., CD28).