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

Cell Rep. 2024 Sep 24;43(9):114690. doi: 10.1016/j.celrep.2024.114690. Epub 2024 Aug 30.

Abstract

During tumorigenesis, the recently identified tumor-specific memory T cells in draining lymph nodes (TdLN-TTSM cells) play a pivotal role in tumor repression that gives rise to progenitor exhausted T (TPEX) cells and further replenishes tumor-specific CD8+ T cells residing in the tumor microenvironment (TME). However, how TTSM 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 TTSM cells compared with other CD8+ T cell subsets. The deficiency of ID3 significantly interrupts the maintenance of TTSM and TPEX 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 TTSM cell population and enhances the anti-tumor immune response.

Keywords: CP:; CP: Immunology; ID3; maintenance; tumor draining lymph node; tumor-specific memory T cell.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD8-Positive T-Lymphocytes* / immunology
  • CD8-Positive T-Lymphocytes* / metabolism
  • Carcinogenesis* / genetics
  • Carcinogenesis* / immunology
  • Carcinogenesis* / pathology
  • Cell Line, Tumor
  • Immunologic Memory
  • Inhibitor of Differentiation Proteins* / genetics
  • Inhibitor of Differentiation Proteins* / metabolism
  • Lymph Nodes* / immunology
  • Lymph Nodes* / metabolism
  • Lymph Nodes* / pathology
  • Memory T Cells / immunology
  • Memory T Cells / metabolism
  • Mice
  • Mice, Inbred C57BL*
  • Tumor Microenvironment / immunology

Substances

  • Inhibitor of Differentiation Proteins
  • Idb3 protein, mouse