The aged tumor microenvironment limits CD8+ T cell control of cancer

As people age, their immune function gradually declines, coinciding with increased cancer rates. However, the precise reasons behind age-related dysfunction of CD8+ T cells in cancer remain unclear. Our study reveals that tumor growth accelerates in older tumor-bearing mice due to diminished infiltration and function of CD8+ T cells. Even when young, tumor antigen-specific CD8+ T cells are transferred into aged hosts, they fail to combat tumors effectively. This failure is related to the rapid onset of CD8+ T cell dysfunction triggered by cell-extrinsic signals from the aged tumor microenvironment. Given that aging is typified by a persistent, low-level inflammation termed inflammaging across various tissues, we wonder whether a specific type of pro-inflammatory cytokine or chemokine is the potential cell-extrinsic signal in the aged tumors that causes CD8+ T cell dysfunction. We then utilize the Olink Target 48 Mouse Cytokine platform to explore the interplay of cytokines and chemokines within both the aging hosts generally and the aged tumors locally. In summary, our research delves into the cell-extrinsic signals (e.g., pro-inflammatory cytokine or chemokine) influencing CD8+ T cell response in aged tumors and proposes potential therapeutic approaches to enhance CD8+ T cell control of cancer.  Learning Objectives  •Understand the potential mechanism of how the aged tumor microenvironment limits CD8+ T cell control of cancer. •Discover proper therapeutic approaches to reinvigorate CD8+ T cell effector function in aged tumors. •