CD4 and cancer: This points to a general need for caution when extrapolating to human cancer based on evidence from these pre-clinical models, where the specific biological contribution and mechanisms utilized by cytotoxic CD4+ T cells in anti-tumor immunity may depend on the specific tumor type and its associated mutational burden or characteristics as well as the specific immunotherapeutic agent(s) administered and the amount of immunologic space that drives the development of these cytotoxic cells (e.g., lymphopenic versus immunocompetent).