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