Both cancer and aging affect the activity of T cells in the adaptive immune system, leading to exhaustion and senescence. This poses challenges for immunotherapies utilizing engineered T cells, as well as for the aging population. Enhancing T cell resilience to combat the effects of aging and cancer is a promising goal, but requires a deeper understanding of T cell exhaustion.
Cellular immunotherapy is transforming cancer treatment by leveraging T cells to target metastatic cancer. However, T cells can succumb to exhaustion or senescence, hindering the success of these therapies. Researchers are working to enhance T cell functionality and resilience to overcome these obstacles.
T cells are evolutionarily programmed to dampen their function in chronic infections to prevent autoimmunity. Chronic activation can drive T cells towards senescence and exhaustion, weakening the immune response to cancer. Researchers are exploring checkpoint inhibitors and engineered T cells to address these challenges successfully in some cases.
A synthetic T cell state known as TIF has been developed by disrupting the BCOR and ZC3H12A genes. This approach aims to create T cells with enhanced longevity and anti-tumor capabilities. TIF cells demonstrate improved survival, enter a reversible dormant state like memory cells, and show enhanced therapeutic efficacy by removing brakes on T cell programs.
Link: https://doi.org/10.1084/jem.20240258
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