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.