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Cancer vaccines as enablers of immunotherapy
Samir N Khleif1,2, Seema Gupta3
1Center for Advanced Immunotherapy Research, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC, USA. snk48@georgetown.edu.
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.
Insights
Cancer vaccines are emerging to improve immunotherapy by enhancing T cell responses against tumors. Integrating vaccines into treatment regimens may broaden immunotherapy benefits for more patients.
Area of Science:
- Oncology
- Immunology
- Vaccinology
Background:
- Immunotherapy has revolutionized cancer treatment but faces challenges with patient response and resistance.
- A key limitation is the lack of effective tumor-specific T cell responses, especially in non-immunogenic tumors with immunosuppressive microenvironments.
Purpose of the Study:
- To review the immunobiology of T cell priming in cancer.
- To define the role of cancer vaccines in overcoming immune evasion.
- To outline principles for designing next-generation vaccine-based combination therapies.
Main Methods:
- Synthesis of current knowledge on cancer immunotherapy and vaccine development.
- Analysis of genomic and computational neoantigen prediction advancements.
- Review of immunobiology and mechanisms of immune evasion.
Main Results:
- Cancer vaccines can restore T cell priming, broaden neoantigen specificity, and convert 'cold' tumors to 'hot'.
- Advances in genomics and neoantigen prediction are revitalizing cancer vaccine research.
Conclusions:
- Cancer vaccines show promise as enablers of immunotherapy, addressing key barriers to durable efficacy.
- Integrating vaccines into immunotherapy regimens, guided by immune contexture and antigen selection, could expand treatment benefits to a wider patient population.
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