ICOS and melanoma: Intriguingly, it has been reported that response to immunotherapy is exceptionally challenging due to the fact that EOC tumors exhibit elevated levels of highly activated Tregs (31), with a distinct phenotype exhibiting higher levels of FOXP3, PD-1, 4-1BB, and ICOS compared to melanoma tumoral Tregs, while also displaying increased suppressive capabilities against cytotoxic T cell proliferation (34).