CD4 and neoplasm: While PD-(L)1-directed ICI therapies, as a standard-of-care treatment for several tumor types, critically depend on CTL-mediated immune responses 55-57, emerging ICI combinations, including CTLA-4, Lag-3, or OX40-targeting mAbs, along with innovative tumor vaccination approaches, emphasize the increasing focus on reinvigorating antitumoral CD4+ T-cell activity 31, 56-59.