The human body undergoes considerable changes as it ages, and the immune system is no exception. Aging of the immune system leads to a decline in the body's overall immune function. There is now growing evidence suggesting that the effectiveness of cancer immunotherapy also diminishes with age. Yet, the exact relationship between immune system aging and the effectiveness of cancer immunotherapy is unclear. Furthermore, identification of a strategy to "rejuvenate" an aging immune system would have significant impact on the treatment of cancer and other human diseases. Our group recently found that aged animals respond to immune checkpoint inhibitors to a lesser extent when compared to young a...

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The human body undergoes considerable changes as it ages, and the immune system is no exception. Aging of the immune system leads to a decline in the body's overall immune function. There is now growing evidence suggesting that the effectiveness of cancer immunotherapy also diminishes with age. Yet, the exact relationship between immune system aging and the effectiveness of cancer immunotherapy is unclear. Furthermore, identification of a strategy to "rejuvenate" an aging immune system would have significant impact on the treatment of cancer and other human diseases. Our group recently found that aged animals respond to immune checkpoint inhibitors to a lesser extent when compared to young animals harboring genetically identical tumors. This reduced antitumor response was associated with a similar decline in the number of tumor-infiltrating T cells in aged animals. We also found an association between T cell infiltration and the presence of specific macrophages, an innate immune cell that has previously been identified to help T cell recruitment, into tumors. The number of these macrophages were also found to be diminished in aged animals. Based on these results, we hypothesize that aging diminishes the ability for T cells to enter tumors, largely due to corresponding decline in the presence of specific macrophages. Restoring T cell infiltration by increasing the presence of these macrophages in tumors in aged mice will results in more responsiveness to cancer immunotherapies such as immune checkpoint blockade. If successfully completed, our study will drastically advance our current understanding of the relationship between immune system aging and the response of cancer immunotherapies and provide a completely new framework that links the two through a yet to be discovered mechanism. Importantly, our study could lead to the Identification of potential ways to "rejuvenate" an aging immune system to improve therapy responses that will have direct impact on patients.

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