by Mary Anne Dunkin MATHER, CA—Cancer is a major health concern for U.S. veterans, many of whom face elevated risks due to age and prior environmental or occupational exposures. Lung cancer, in particular, is a leading cause of cancer-related death in the veteran population, driven in part by higher rates of smoking and potential exposure to carcinogens such as burn pits, asbestos and other environmental haz- ards during military service.¹ Within the VA, improving outcomes for patients with lung cancer is a critical priority. Despite advances in treat- ment, lung cancer continues to pose significant clinical challenges across the VA health system. A recent review published in the Journal of Hematology & Oncology pointed to cancer vaccines as a promising strategy to address one of the most persistent challenges in oncology: resistance to immunotherapy. The study high- lighted emerging vaccine approaches designed to enhance the effectiveness of immune checkpoint inhibitors (ICIs) and overcome treatment resistance in lung cancer. While the review was not sponsored by the VA, two of its authors are affiliated with the VA Northern California Health Care System in Mather, CA, reflecting the VA’s broader role in advancing cancer research.² Over the past decade, ICIs have improved outcomes for some patients by restoring the immune system’s ability to recognize and attack tumor cells. These therapies target regulatory pathways such as PD-1, PD-L1 and CTLA-4, releasing inhibitory signals on T cells and enabling anti- tumor responses. However, resistance—either primary or acquired—remains a major clinical challenge.² Real-world data from the VA illustrated both the prog- ress and limitations of the therapies. In a large retrospec- tive analysis of more than 27,000 veterans treated between 2010 and 2023, ICIs were associated with improved sur- vival across multiple cancer types, including lung can- cer, although outcomes varied by patient and disease characteristics.³ According to the new review led by researchers from the Department of Medicine at the University of Missouri, in Columbia, resistance to ICIs involve “multiple, often overlapping processes, including inadequate tumor antigen presentation, dysfunctional T-cell priming and expansion, Cancer Vaccines in Lung Cancer: A New Strategy to Overcome Immunotherapy Resistance Immune checkpoint inhibitor (ICI) resistance can be caused by tumor evasion mechanisms that prevent T cells from recognizing or killing cancer cells. Cancer vaccines are designed to address those challenges 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 maintaining a favorable safety profile,” according to a new study. 6 8
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