The transcription regulator ID3 maintains tumor-specific memory CD8+ T cells in draining lymph nodes during tumorigenesis

During tumorigenesis, the recently identified tumor-specific memory T cells in draining lymph nodes (TdLN-T_TSM cells) play a pivotal role in tumor repression that gives rise to progenitor exhausted T (T_PEX) cells and further replenishes tumor-specific CD8⁺ T cells residing in the tumor microenvironment (TME). However, how T_TSM cells are maintained in TdLN is largely unknown. Here, we show that the transcription regulator ID3 (inhibitor of DNA binding 3) is highly expressed by T_TSM cells compared with other CD8⁺ T cell subsets. The deficiency of ID3 significantly interrupts the maintenance of T_TSM and T_PEX cells, resulting in decreased tumor-infiltrating CD8⁺ T cells and impaired tumor control. Consistent with this, overexpression of ID3 in CD8⁺ T cells increases the T_TSM cell population and enhances the anti-tumor immune response.