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Jansen, Caroline S; Prokhnevska, Nataliya; Master, Viraj A; Sanda, Martin G; Carlisle, Jennifer W; Bilen, Mehmet Asim; Cardenas, Maria; Wilkinson, Scott; Lake, Ross; Sowalsky, Adam G; Valanparambil, Rajesh M; Hudson, William H; McGuire, Donald; Melnick, Kevin; Khan, Amir I; Kim, Kyu; Chang, Yun Min; Kim, Alice; Filson, Christopher P; Alemozaffar, Mehrdad; Osunkoya, Adeboye O; Mullane, Patrick; Ellis, Carla; Akondy, Rama; Im, Se Jin; Kamphorst, Alice O; Reyes, Adriana; Liu, Yuan; Kissick, Haydn
Nature, 12/2019, Letnik: 576, Številka: 7787Journal Article
Tumour-infiltrating lymphocytes are associated with a survival benefit in several tumour types and with the response to immunotherapy . 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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in: SICRIS
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