This leads to a tentative conclusion – the existence of anti-tumor CD8 T cells expressing HELIOS – and raises three hypotheses (1): the existence of HLA-E-restricted anti-tumor CD8 T cells since we demonstrated that only HLA-E-restricted CD8 T cells express HELIOS (2); HELIOS expression in some exhausted TOXhi CD8 TILs independent of HLA-E restriction (3); a combination of both possibilities. The gene discussed is CD8A; the disease is neoplasm.