期刊
NATURE
卷 576, 期 7787, 页码 465-+出版社
NATURE RESEARCH
DOI: 10.1038/s41586-019-1836-5
关键词
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资金
- Prostate Cancer Foundation
- Swim Across America
- James M. Cox Foundation
- Winship Cancer Institute - Dunwoody Country Club Senior Men's Association
- NCI [1-R00-CA197891, U01-CA113913]
- NIH [P51 OD011132]
- Emory Flow Cytometry Core - National Center for Georgia Clinical & Translational Science Alliance of the National Institutes of Health [UL1TR002378]
- Intramural Research Program of the NIH, National Cancer Institute
- Emory University Integrated Cellular Imaging Microscopy Core of the Winship Cancer Institute of Emory University
- NIH/NCI [2P30CA138292-04]
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.
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