Cancer vaccines as enablers of immunotherapy.

Abstract

Immunotherapy has transformed cancer care, but most patients do not respond and ultimately develop resistance. A central barrier to durable efficacy is the absence of robust, tumor-specific T cell responses, particularly in tumors characterized by low antigenicity and an immunosuppressive tumor microenvironment. Cancer vaccines, long explored with limited clinical success as monotherapies, are emerging as enablers of immunotherapy by restoring T cell priming, broadening neoantigen-specific repertoires and converting tumors from 'cold' to 'hot'. Advances in genomics and computational neoantigen prediction have reinvigorated the field. In this Review, we synthesize current knowledge on the immunobiology of T cell priming in cancer, define how cancer vaccines can address the multifaceted mechanisms of immune evasion, and outline principles for designing next-generation vaccine-based combinations. We also propose that integration of vaccines into immunotherapy regimens, guided by tumor-specific immune contexture, antigen selection and treatment sequencing, might expand the benefit of immunotherapy to a broader patient population.