An intra-tumoral niche maintains and differentiates stem-like CD8 T cells

Nature. 2019 Dec;576(7787):465-470. doi: 10.1038/s41586-019-1836-5. Epub 2019 Dec 11.


Tumour-infiltrating lymphocytes are associated with a survival benefit in several tumour types and with the response to immunotherapy1-8. However, the reason some tumours have high CD8 T cell infiltration while others do not remains unclear. Here we investigate the requirements for maintaining a CD8 T cell response against human cancer. We find that CD8 T cells within tumours consist of distinct populations of terminally differentiated and stem-like cells. On proliferation, stem-like CD8 T cells give rise to more terminally differentiated, effector-molecule-expressing daughter cells. For many T cells to infiltrate the tumour, it is critical that this effector differentiation process occur. In addition, we show that these stem-like T cells reside in dense antigen-presenting-cell niches within the tumour, and that tumours that fail to form these structures are not extensively infiltrated by T cells. Patients with progressive disease lack these immune niches, suggesting that niche breakdown may be a key mechanism of immune escape.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigen Presentation / genetics
  • Antigen Presentation / immunology
  • CD8-Positive T-Lymphocytes / cytology*
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / metabolism
  • Cell Differentiation*
  • Disease Progression
  • Epigenesis, Genetic
  • Hepatocyte Nuclear Factor 1-alpha / metabolism
  • Humans
  • Lymphocytes, Tumor-Infiltrating / cytology*
  • Lymphocytes, Tumor-Infiltrating / immunology*
  • Lymphocytes, Tumor-Infiltrating / metabolism
  • Mice
  • Neoplasms / immunology*
  • Neoplasms / pathology
  • Stem Cell Niche / immunology
  • Stem Cells / cytology*
  • Transcription, Genetic
  • Tumor Escape / genetics
  • Tumor Escape / immunology


  • HNF1A protein, human
  • Hepatocyte Nuclear Factor 1-alpha