These activities include (1) blockade of the CTLA-4 checkpoint, resulting in the induction of non-canonical CD4+ T cell subsets (i.e., Tbet+ICOS+ Th1-like CD4+ T cells)22 and the priming of novel CD8+ T cell clonotypes in the periphery,21 (2) Fc-dependent depletion of FOXP3+ Tregs in tumors27 and inhibition of their immunosuppressive function,42 and (3) Fc-dependent remodeling of tumor blood vessels and increase of TA-HEVs. The gene discussed is ICOS; the disease is neoplasm.