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


Tumour-infiltrating lymphocytes are associated with a survival benefit in several tumour types and with the response to immunotherapy<sup>1-8</sup>. 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.

  • Akondy R
  • Alemozaffar M
  • Bilen MA
  • Cardenas M
  • Carlisle JW
  • Chang YM
  • Ellis C
  • Filson CP
  • Hudson WH
  • Im SJ
  • Jansen CS
  • Kamphorst AO
  • Khan AI
  • Kim A
  • Kim K
  • Kissick H
  • Lake R
  • Liu Y
  • Master VA
  • McGuire D
  • Melnick K
  • Mullane P
  • Osunkoya AO
  • Prokhnevska N
  • Reyes A
  • Sanda MG
  • Sowalsky AG
  • Valanparambil RM
  • Wilkinson S
PubMed ID
Appears In
Nature, 2019, 576 (7787)