| Literature DB >> 31827286 |
Caroline S Jansen1, Nataliya Prokhnevska1, Viraj A Master1,2, Martin G Sanda1,2, Jennifer W Carlisle2,3, Mehmet Asim Bilen2,3, Maria Cardenas1, Scott Wilkinson4, Ross Lake4, Adam G Sowalsky4, Rajesh M Valanparambil5,6, William H Hudson5,6, Donald McGuire5,6, Kevin Melnick1, Amir I Khan1, Kyu Kim1, Yun Min Chang5, Alice Kim1, Christopher P Filson1,2, Mehrdad Alemozaffar1,2, Adeboye O Osunkoya1,2,7, Patrick Mullane7, Carla Ellis7, Rama Akondy5,6, Se Jin Im5,6, Alice O Kamphorst8, Adriana Reyes1, Yuan Liu2,9, Haydn Kissick10,11,12,13.
Abstract
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.Entities:
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Year: 2019 PMID： 31827286 PMCID： PMC7108171 DOI： 10.1038/s41586-019-1836-5
Source DB: PubMed Journal: Nature ISSN： 0028-0836 Impact factor: 49.962