Open AccessAn intra-tumoral niche maintains and differentiates stem-like CD8 T cells
Author(s) -
Caroline S. Jansen,
Nataliya Prokhnevska,
Viraj A. Master,
Martin G. Sanda,
Jennifer Carlisle,
Mehmet Asım Bilen,
Maria Cardenas,
Scott Wilkinson,
Ross Lake,
Adam G. Sowalsky,
Rajesh M. Valanparambil,
William Henry Hudson,
Donald J. McGuire,
Kevin Melnick,
Alamzeb Khan,
Kyu Kim,
Yun Min Chang,
Alice Kim,
Christopher P. Filson,
Mehrdad Alemozaffar,
Adeboye O. Osunkoya,
Patrick Mullane,
Carla LaShan Ellis,
Rama Akondy,
Se Jin Im,
Alice O. Kamphorst,
Adriana Moon Reyes,
Yuan Liu,
Haydn Kissick
Publication year - 2019
Publication title -
nature
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 15.993
H-Index - 1226
eISSN - 1476-4687
pISSN - 0028-0836
DOI - 10.1038/s41586-019-1836-5
Subject(s) - biology , cd8 , cytotoxic t cell , stem cell , immune system , microbiology and biotechnology , immunology , cancer research , genetics , in vitro
Tumour-infiltrating lymphocytes are associated with a survival benefit in several tumour types and with the response to immunotherapy 1-8 . 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.