CTLA4 and colon carcinoma: found that anti-CTLA-4 treatment could repress the growth of murine colon carcinoma and murine fibrosarcoma (32), and more than a decade later anti-CTLA-4 monoclonal antibody ipilimumab was used in phase II and phase III clinical study of advanced melanoma in patients who had undergone previous treatment and was proved to improve both overall survival(OS) and progression-free survival (PFS) (11, 33), and ipilimumab was the first immune checkpoint inhibitor approved by US Food and Drug Administration (FDA) for advanced melanoma in 2011.