TY - JOUR
T1 - An intra-tumoral niche maintains and differentiates stem-like CD8 T cells
AU - Jansen, Caroline S.
AU - Prokhnevska, Nataliya
AU - Master, Viraj A.
AU - Sanda, Martin G.
AU - Carlisle, Jennifer W.
AU - Bilen, Mehmet Asim
AU - Cardenas, Maria
AU - Wilkinson, Scott
AU - Lake, Ross
AU - Sowalsky, Adam G.
AU - Valanparambil, Rajesh M.
AU - Hudson, William H.
AU - McGuire, Donald
AU - Melnick, Kevin
AU - Khan, Amir I.
AU - Kim, Kyu
AU - Chang, Yun Min
AU - Kim, Alice
AU - Filson, Christopher P.
AU - Alemozaffar, Mehrdad
AU - Osunkoya, Adeboye O.
AU - Mullane, Patrick
AU - Ellis, Carla
AU - Akondy, Rama
AU - Im, Se Jin
AU - Kamphorst, Alice O.
AU - Reyes, Adriana
AU - Liu, Yuan
AU - Kissick, Haydn
N1 - Funding Information:
Acknowledgements This work was supported by funding from the Prostate Cancer Foundation, Swim Across America, the James M. Cox Foundation and James C. Kennedy, pilot funding from the Winship Cancer Institute supported by the Dunwoody Country Club Senior Men’s Association, and NCI grants 1-R00-CA197891 (H.K.) and U01-CA113913 (M.G.S.). We recognize Adaptive Biotechnologies for providing laboratory services as a part of an educational grant award. We would like to acknowledge the Yerkes NHP Genomics Core which is supported in part by NIH P51 OD011132, the Emory Flow Cytometry Core supported by the National Center for Georgia Clinical & Translational Science Alliance of the National Institutes of Health under award number UL1TR002378, the Intramural Research Program of the NIH, National Cancer Institute and the Emory University Integrated Cellular Imaging Microscopy Core of the Winship Cancer Institute of Emory University and NIH/NCI under award number 2P30CA138292-04.
Publisher Copyright:
© 2019, The Author(s), under exclusive licence to Springer Nature Limited.
PY - 2019/12/19
Y1 - 2019/12/19
N2 - 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.
AB - 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.
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U2 - 10.1038/s41586-019-1836-5
DO - 10.1038/s41586-019-1836-5
M3 - Article
C2 - 31827286
AN - SCOPUS:85076588925
SN - 0028-0836
VL - 576
SP - 465
EP - 470
JO - Nature
JF - Nature
IS - 7787
ER -
