Immune function progressively declines with age, contributing to the increased incidence and aggressiveness of cancer with aging. Exploring the mechanisms of immune aging, both on a systemic level and within the tumor microenvironment, holds the potential to reveal innovative strategies for cancer immunotherapy.

Aging brings about substantial changes in both systemic and cellular metabolism, and there is growing evidence to suggest that these might interfere with micronutrient availability and with immunometabolism thereby driving the decline in anti-tumor immunity of the elderly.
A notable change associated with aging is the diminished availability of iron, a critical element for the proliferation and effector function of immune cells. The connection between age-related iron dyshomeostasis and the decline in anti-tumor immunity remains largely unexplored.

We possess extensive experience in studying immunometabolism and its role in immune function and inflammation (Vaeth* and Maus*, et al., Immunity, 2017). Recently, we have identified iron dyshomeostasis as a key driver of senescence-associated inflammation and age-related tissue remodeling (Maus et al., Nature Metabolism, 2023), both of which play pivotal roles in tumorigenesis. In this project, our goal is to bridge these fields and address fundamental questions regarding the impact of age, inflammation, and cancer-associated iron dyshomeostasis on the immune system’s ability to prevent and combat cancer. We aim to identify novel approaches for assessing and addressing immune aging, ultimately enhancing anti-tumor immunity in cancer patients.