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

Caroline S. Jansen, Nataliya Prokhnevska, Viraj A. Master, Martin G. Sanda, Jennifer W. Carlisle, Mehmet Asim Bilen, Maria Cardenas, Scott Wilkinson, Ross Lake, Adam G. Sowalsky, Rajesh M. Valanparambil, William H. Hudson, Donald McGuire, Kevin Melnick, Amir I. Khan, Kyu Kim, Yun Min Chang, Alice Kim, Christopher P. Filson, Mehrdad AlemozaffarAdeboye O. Osunkoya, Patrick Mullane, Carla Ellis, Rama Akondy, Se Jin Im, Alice O. Kamphorst, Adriana Reyes, Yuan Liu, Haydn Kissick*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

86 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)465-470
Number of pages6
JournalNature
Volume576
Issue number7787
DOIs
StatePublished - Dec 19 2019
Externally publishedYes

ASJC Scopus subject areas

  • General

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