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

Article

关键词: TERTIARY LYMPHOID STRUCTURES;    ANTI-PD-L1 ANTIBODY;    PD-1 BLOCKADE;    SURVIVAL;    PREDICTOR;    RESPONSES;    DENSITY;    SAFETY;   

DOI  :  10.1038/s41586-019-1836-5

来源: SCIE

【 摘 要 】

Tumour-infiltrating lymphocytes are associated with a survival benefit in several tumour types and with the response to immunotherapy(1-8). 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.

【 授权许可】

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