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

By Caroline S. Jansen, Nataliya Prokhnevska, V. Master, M. Sanda, J. Carlisle, M. Bilen, M. Cardenas, S. Wilkinson, Ross Lake, A. Sowalsky and 19 more. Nature, 2019

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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. The authors examine the immune cell infiltrates of human tumours and provide evidence for a population of CD8 T cells with stem-cell characteristics and proliferative capacity that reside in an antigen-presenting niche within tumours.

Subfields: Immunology, Oncology

View Paper: https://www.semanticscholar.org/paper/e5bc404bf23e5d04f730ed14434f2908a8062f27

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