TNF and neoplasm: In addition to immune checkpoints, the number of CD4- and CD8-positive T-cells (121, 122) and the presence of costimulatory signaling molecules (64), namely OX40 (member 4 of tumor necrosis factor [TNF] family) and GITR (glucocorticoid-induced TNF Receptor), in the tumor microenvironment impact the response to immunotherapy.