Activation of ICOS was first known to enhanced T-cell proliferation.90,91 Interestingly, preclinical studies demonstrated that ICOS was upregulated following anti-CTLA-4 treatment in tumor bearing murine models, suggesting that it could be an important mediator of better T-cell responses in the anti-CTLA-4 treated patients.92,93. Here, ICOS is linked to neoplasm.