期刊
NATURE
卷 592, 期 7852, 页码 138-+出版社
NATURE PORTFOLIO
DOI: 10.1038/s41586-021-03368-8
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资金
- Intramural Research Programs of the National Cancer Institute
- Israel Science Foundation [1435/16]
- European Research Council (ERC) under the European Union's Horizon 2020 research and innovation programme [770854]
- Rising Tide Foundation
- Henry Chanoch Krenter Institute for Biomedical Imaging and Genomics
- Estate of Alice Schwarz-Gardos
- Estate of John Hunter
- Knell Family
- Peter and Patricia Gruber Award
- Hamburger Family
- Wellcome Sanger [WT098051]
- NIH NIAID [K01AI143881]
- CCSG NIH NCI grant [CA016672]
- MRA [622106]
- Joel and Mady Dukler Fund for Cancer Research
- Hadar Impact Fund
- Fannie Sherr Fund
- Erica Drake Fund
- European Research Council (ERC) [770854] Funding Source: European Research Council (ERC)
The study found that peptides derived from intracellular bacteria can be presented by tumor cells, eliciting an immune response and shedding light on how bacteria influence immune activation and therapy responses.
A variety of species of bacteria are known to colonize human tumours(1-11), proliferate within them and modulate immune function, which ultimately affects the survival of patients with cancer and their responses to treatment(12-14). However, it is not known whether antigens derived from intracellular bacteria are presented by the human leukocyte antigen class I and II (HLA-I and HLA-II, respectively) molecules of tumour cells, or whether such antigens elicit a tumour-infiltrating T cell immune response. Here we used 16S rRNA gene sequencing and HLA peptidomics to identify a peptide repertoire derived from intracellular bacteria that was presented on HLA-I and HLA-II molecules in melanoma tumours. Our analysis of 17 melanoma metastases (derived from 9 patients) revealed 248 and 35 unique HLA-I and HLA-II peptides, respectively, that were derived from 41 species of bacteria. We identified recurrent bacterial peptides in tumours from different patients, as well as in different tumours from the same patient. Our study reveals that peptides derived from intracellular bacteria can be presented by tumour cells and elicit immune reactivity, and thus provides insight into a mechanism by which bacteria influence activation of the immune system and responses to therapy.
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