HIS- and patient-derived CD4 CTLs both associated with tumor growth control: in melanoma patients, a CD4 cluster co-expressing CXCL13 and cytotoxic genes was associated with better overall survival;57 in colorectal cancer patients, a GZMB+ Th1-like CD4 subset was enriched in PD1-responding MSI tumors;24 in bladder cancer patients, a gene signature of cytotoxic CD4 T cells in tumors predicted clinical response to anti-PD-L1 treatment;56 and in our model, increased CD4 CTLs in blood and tumors associated with potent tumor control, including complete tumor rejection. This evidence concerns the gene CD4 and melanoma.