2 0 2 6 C O M P E N D I U M O F F E D E R A L M E D I C I N E 6 9 and the presence of physical and immunosuppressive barri- ers within the tumor microenvironment that limit immune cell infiltration and effector function.” Cancer vaccines are designed to address those chal- lenges by stimulating the immune system to recognize tumor-specific antigens. Unlike preventive vaccines, these therapeutic approaches can “induce de novo or amplify pre-existing tumor-specific immune responses, thereby enhancing long-term immunological memory while main- taining a favorable safety profile,” the authors wrote. Advances in genomics and bioinformatics have accel- erated progress in this field. Next-generation sequencing enables identification of tumor-specific mutations, or neo- antigens, that can serve as precise vaccine targets, while computational tools help predict which are most likely to trigger a strong immune response.² Personalized neoantigen vaccines, tailored to an indi- vidual patient’s tumor, have shown particular promise. Advances in mRNA technology enable more rapid vac- cine design and production, and early studies suggest these vaccines can generate robust T-cell responses and encour- aging clinical outcomes. However, manufacturing remains complex and time-consuming, which may limit use in rap- idly progressing disease.² In contrast, off-the-shelf vaccines target shared tumor antigens and can be produced at scale, making them more accessible and cost-effective. While potentially less precise, they offer practical advantages that may support broader clinical implementation. The authors also highlighted the importance of timing, noting that cancer vaccines may be “more effective in the adjuvant setting than in the metastatic setting, where high tumor burden and an immunosuppressive tumor microenvironment constrain vaccine-induced immune responses.”² Importantly, cancer vaccines are unlikely to succeed as standalone therapies. Combination strategies—particularly with ICIs—are a major focus. Vaccines can prime and expand tumor-specific T cells, while checkpoint inhibitors enhance their activity by removing inhibitory signals. As the authors note, these approaches aim to “enhance T-cell activation, reverse immune sup- pression, and restore antitumor immunity.”² Researchers also are exploring combinations with therapies targeting the tumor microenvironment, includ- ing regulatory T cells, myeloid-derived suppressor cells and tumor-associated macrophages, to address multiple barriers simultaneously.² Despite progress, challenges remain. Identifying truly immunogenic neoantigens is difficult, and immune responses observed in laboratory settings do not always translate into meaningful clinical benefit. Improved tools and biomarkers are needed to guide treatment selection and evaluate response.² As research continues, cancer vaccines are increas- ingly viewed as a promising component of next-generation immunotherapy strategies—designed to overcome resis- tance and extend treatment benefits for patients with lung cancer, including veterans.² 1Lewis JA, Stranick A, Pennings J, Samuels LR, et al. National Survey of Lung Cancer Screening Eligibility in United States Veterans. Am J Prev Med. 2025 May;68(5):886-895. doi: 10.1016/j.amepre.2025.01.015. Epub 2025 Jan 27. PMID: 39880059; PMCID: PMC12033076. 2Tang Z, Zha L, Liang R, Li T. Lung cancer vaccines to enhance immune checkpoint inhibitor therapy: evidence and future perspectives. J Hematol Oncol. 2026 Feb 3;19(1):15. doi: 10.1186/s13045-026-01778-7. PMID: 41634728; PMCID: PMC12896110. 3Miller SR, Schipper M, Fritsche LG, Jiang R, Strohbehn G, et al. Pan- Cancer Survival Impact of Immune Checkpoint Inhibitors in a National Healthcare System. Cancer Med. 2024 Nov;13(21):e70379. doi: 10.1002/ cam4.70379. PMID: 39508134; PMCID: PMC11541111. Cancer statistics, 2025. Source: Siegel RL, Kratzer TB, Giaquinto AN, Sung H, Jemal A. Cancer statistics, 2025. CA Cancer J Clin. 2025;75(1):10-45.
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