Cancer vaccines as enablers of immunotherapy16 Oct 2025 20:04
Https://www.nature.com/articles/s41590-025-02308-2
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.
Conclusions
T cell infiltration into the TME is paramount for an effective antitumor
immune response. Priming and activation of T cells are critical factors
that enable infiltration into the TME. Many factors leading to suboptimal T cell priming can be addressed with properly designed vaccines.
Thus, therapeutic cancer vaccines are a promising strategy for reversing
the conditions that create a T cell-deprived TME. By optimizing the TME,
these vaccines enhance the antitumor immune response and function
as immunotherapy enablers. This approach can potentially overcome
immunotherapy resistance and improve cancer therapeutic outcomes.
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