ICOS-modulating agents such as KY1044 have shown promise in activating “cold tumors” to increase T-cell infiltration and decrease Tregs, thereby creating a tumor microenvironment more amenable to an antitumor immune response.30 A prior study found that inhibition of ICOS signaling before PD-1 immunotherapy, thereby interrupting the intratumor CD8+ T cell and Treg crosstalk, can improve the efficacy of PD-1-directed therapy.34 Thus, ICOS-directed therapies may play an important role in circumventing immunotherapy resistance for combination therapy. The gene discussed is ICOS; the disease is neoplasm.