ICOS and melanoma: Bhlhe40 has been shown to promote Th1 cells,88–90 and subsets of Bhlhe40+ Th1-like CD4 T cells were found to be enriched in patients with colorectal cancer with microsatellite instability, which display more favorable outcomes in response to anti-CTLA-4.91 Further, studies in both preclinical models and patients with melanoma revealed that anti-CTLA-4 induces ICOS+ CD4 T cells expressing IFN-g,65,66 together suggesting the human relevance of our findings.