HLA-G and neoplasm: Interestingly, a recent in vitro study provided strong evidence that the presence of sHLA-G prior to T cell activation leads to an increase in ILT-2 expression as well as co-expression of other immune checkpoints such as CTLA4, PD-1, and CD95 on CD8+ T cells, suggesting a distinct immunosuppressive/exhausted phenotype of CD8+ T cells, thereby potentially subverting tumor cell immune surveillance (48).