Interestingly, when a stimulatory ICOS antibody was used in combination with anti-CTLA-4, there was a significant improvement in tumor rejection in both melanoma and colon cancer mouse models, suggesting that HPV(+) tumors expressing high levels of ICOSLG may respond better to anti-CTLA-4 therapy [35]. This evidence concerns the gene CTLA4 and malignant colon neoplasm.