Notably, both GITRL and 4-1BBL send signals that impair direct and antibody-induced NK cell cytotoxicity and IFNγ production [205,209], suggesting that both GITR/GITRL and 4-1BB/4-1BBL interactions may contribute to CLL pathophysiology and resistance to immunotherapy. This evidence concerns the gene TNFRSF9 and B-cell chronic lymphocytic leukemia.