Aging as a Driver of Immune Dysfunction in Cancer

James (SeongJun) Han, PhD
Postdoctoral Fellow
Departments of Immunology and Cell Biology
Harvard Medical School
Blavatnik Institute
Boston, MA, USA  

This conference is hosted by Nathalie Labrecque, PhD. This conference is part of the the IRCM Early-Career Scientist Seminar Series (ECS³), a groundbreaking initiative whose mission is to showcase early career scientists. This is a great opportunity to discover the exciting projects of these researchers in training in front of a multidisciplinary audience.

About the conference
Aging profoundly reshapes host biology and is strongly linked to the onset of age-related diseases including cancer. While the immune system plays a central role in regulating tumor progression, how aging alters T cell populations and functions in this context remains poorly understood. To address this, we established a genetically engineered mouse model of lung adenocarcinoma to examine how T cell populations and function change with age. We found that aging profoundly reprograms CD8⁺ T cells, driving metabolic changes that impair their anti-tumor activity and promote tumor growth. Integrated transcriptomic and metabolomic analyses revealed that these metabolic alterations enhance immune suppression and limit the capacity of T cells to mount effective responses. Importantly, targeting these metabolic pathways attenuated immune suppression and improved tumor control in aged mice. To extend these findings to humans, we analyzed immune profiles of lung cancer patients treated with anti-PD1 therapy and uncovered associations between aging, altered T cell states, and therapeutic outcomes. Together, our study explores how aging reshapes T cell immunity in cancer and highlight metabolic reprogramming as a therapeutic strategy to improve immunotherapy outcomes in older patients.

About James Han
Dr. James SeongJun Han is a CIHR Banting fellow specializing in aging and cancer immunology research in the laboratories of Drs. Arlene Sharpe and Marcia Haigis at Harvard University. His research investigates how aging reprograms CD8⁺ T cell immunity, with a particular focus on how age-related metabolic dysfunction constrains anti-tumor T cell responses and host response to immunotherapy. Through these studies, Dr. Han aims to establish new paradigms that inform the development of next-generation immunotherapies. Prior to his postdoctoral training, he earned his PhD in Immunology at the University of Toronto and under the mentorship of Dr. Pamela Ohashi.

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