CD4 and neoplasm: With respect to immunomodulatory vaccines, the IDO/PD-L1 peptide vaccine (IO102/IO103) in combination with Nivolumab can elicit IDO/PD-L1-specific CD4+ and CD8+ T cell responses, targeting and eliminating immunosuppressive IDO+/PD-L1+ cells and converting the tumor microenvironment from “cold” to “hot.” This strategy achieved an ORR of up to 80% and a CR rate of 43%, offering a novel immunotherapeutic avenue for brain metastases (67).