期刊
CELL
卷 182, 期 3, 页码 655-+出版社
CELL PRESS
DOI: 10.1016/j.cell.2020.06.001
关键词
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资金
- Team Award from the American Cancer Society [MRAT-18-113-01]
- Melanoma Research Alliance [597698]
- NIH [R01 CA238039, P01 CA163222, T32CA207021]
- National Institutes of Health Mentored Clinical Scientist Development Award [1K08DK114563-01]
- American Gastroenterological Association Research Scholars Award
Checkpoint blockade with antibodies specific for the PD-1 and CTLA-4 inhibitory receptors can induce durable responses in a wide range of human cancers. However, the immunological mechanisms responsible for severe inflammatory side effects remain poorly understood. Here we report a comprehensive single-cell analysis of immune cell populations in colitis, a common and severe side effect of checkpoint blockade. We observed a striking accumulation of CD8 T cells with highly cytotoxic and proliferative states and no evidence of regulatory T cell depletion. T cell receptor (TCR) sequence analysis demonstrated that a substantial fraction of colitis-associated CD8 T cells originated from tissue-resident populations, explaining the frequently early onset of colitis symptoms following treatment initiation. Our analysis also identified cytokines, chemokines, and surface receptors that could serve as therapeutic targets for colitis and potentially other inflammatory side effects of checkpoint blockade.
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