These multi-marker approaches contribute more comprehensive information to the cancer immunity cycle [38] than a single analyte and could improve personalized combination immunotherapy treatment options in patients that have failed prior immunotherapy by targeting over-expressed immunomodulatory factors, including LAG-3, GITR, ICOS, TIM-3, and OX40 [39] across multiple tumor types [40, 41]. This evidence concerns the gene ICOS and cancer.