MHC-II vaccine ignites cold tumors while lighting up TIGIT as a compensatory brake.
Song et al. systematically characterize how an MHC-II-restricted neoantigen vaccine remodels the cold tumor microenvironment. The vaccine promotes T cell infiltration and effector function while upregulating the PVR-TIGIT checkpoint axis. Combining vaccination with TIGIT blockade achieves synergistic anti-tumor efficacy by enhancing antigen-specific CD4 T cell function and delaying exhaustion, providing a promising strategy to overcome immunotherapy resistance in cold tumors.