Samuel C. Markson, PhD, CRI Immuno-Informatics Fellow Harvard Medical School Area of Research: All Cancers, Colorectal Cancer, Melanoma Dr. Markson is investigating age-related changes in “killer” T cells and how that influences our ability to mount successful anti-cancer immune responses as we grow older. Cancer is strongly associated with aging, driven in part by age-related changes in the immune system. Checkpoint inhibitor immunotherapies, which use the immune system to fight cancer, have provided durable responses in patients older than 70 years, but, as in younger patients, less than half of patients either fail to respond or relapse after initially responding. Thus, there is a significant unmet need to discover new immunotherapeutic targets and combination therapies to extend the benefit of immunotherapy to more cancer patients. Dr. Markson’s project focuses on “killer” T cells that directly recognize and eliminate tumor cells. While essential for immunotherapy success, these T cells become functionally compromised as we age. To understand how age-related changes affect killer T cells, Dr. Markson will use cutting-edge gene-editing technology as well as novel algorithms to track immune cells between organs and over time. By identifying specific genes that are expressed differently by killer T cells in older people, he hopes to better understand how immunotherapy acts differently in the elderly and whether certain features of T cell aging could be avoided or reversed to improve outcomes. Overall, the results of his study will inform strategies and identify novel therapeutic targets for improving cancer immunotherapy outcomes in the elderly. Projects and Grants Interrogating mechanisms of aging-associated CD8+ T cell dysfunction and resistance to PD-1 inhibitors in tumors Harvard Medical School | All Cancers, Melanoma, Colorectal Cancer | 2023 | Arlene H. Sharpe, PhD
