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Identification of bacteria-derived HLA-bound peptides in melanoma | Nature
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A variety of species of bacteria are known to colonize human tumours1–11, proliferate within them and modulate immune function, which ultimately affects the survival of patients with cancer and their responses to treatment12–14. 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. HLA peptidomic analysis identifies recurrent intracellular bacteria-derived peptides presented on HLA-I and HLA-II molecules in melanoma tumours, revealing how bacteria can modulate immune functions and responses to cancer therapies.
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headline:Identification of bacteria-derived HLA-bound peptides in melanoma
description:A variety of species of bacteria are known to colonize human tumours1â11, proliferate within them and modulate immune function, which ultimately affects the survival of patients with cancer and their responses to treatment12â14. 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. HLA peptidomic analysis identifies recurrent intracellular bacteria-derived peptides presented on HLA-I and HLA-II molecules in melanoma tumours, revealing how bacteria can modulate immune functions and responses to cancer therapies.
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headline:Identification of bacteria-derived HLA-bound peptides in melanoma
description:A variety of species of bacteria are known to colonize human tumours1â11, proliferate within them and modulate immune function, which ultimately affects the survival of patients with cancer and their responses to treatment12â14. 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. HLA peptidomic analysis identifies recurrent intracellular bacteria-derived peptides presented on HLA-I and HLA-II molecules in melanoma tumours, revealing how bacteria can modulate immune functions and responses to cancer therapies.
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Cancer genetics
Mass spectrometry
Melanoma
Science
Humanities and Social Sciences
multidisciplinary
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name:Kun Wang
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address:
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affiliation:
name:Weizmann Institute of Science
address:
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address:
name:Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel
type:PostalAddress
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name:Garold Fuks
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address:
name:Department of Physics of Complex Systems, Weizmann Institute of Science, Rehovot, Israel
type:PostalAddress
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name:Neerupma Bhardwaj
affiliation:
name:Technion â Israel Institute of Technology
address:
name:The Ruth and Bruce Rappaport Faculty of Medicine, Technion â Israel Institute of Technology, Haifa, Israel
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name:Alexandre Reuben
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affiliation:
name:The University of Texas MD Anderson Cancer Center
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name:Leandro Hermida
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name:National Institutes of Health (NIH)
address:
name:Cancer Data Science Laboratory (CDSL), National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, USA
type:PostalAddress
type:Organization
name:Sarah B. Johnson
affiliation:
name:The University of Texas MD Anderson Cancer Center
address:
name:Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, USA
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name:The University of Texas MD Anderson Cancer Center
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name:Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, USA
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name:Texas A&M University
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name:William C. Shropshire
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name:Cara Haymaker
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address:
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name:Weizmann Institute of Science
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affiliation:
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address:
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affiliation:
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affiliation:
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address:
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affiliation:
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address:
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type:PostalAddress
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name:Jennifer A. Wargo
url:http://orcid.org/0000-0003-3438-7576
affiliation:
name:The University of Texas MD Anderson Cancer Center
address:
name:Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, USA
type:PostalAddress
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name:The University of Texas MD Anderson Cancer Center
address:
name:Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, USA
type:PostalAddress
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name:Ravid Straussman
url:http://orcid.org/0000-0002-9476-329X
affiliation:
name:Weizmann Institute of Science
address:
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name:Yardena Samuels
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affiliation:
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email:[email protected]
PostalAddress:
name:Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel
name:Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel
name:Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel
name:Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel
name:Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel
name:Department of Biology, Technion â Israel Institute of Technology, Haifa, Israel
name:Division of Molecular Oncology and Immunology, The Netherlands Cancer Institute, Amsterdam, The Netherlands
name:Cancer Data Science Laboratory (CDSL), National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, USA
name:Wellcome Sanger Institute, Cambridge, UK
name:Department of Mathematics and Computer Science, Open University of Israel, Raanana, Israel
name:Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel
name:Department of Computer Science and Applied Mathematics, Weizmann Institute of Science, Rehovot, Israel
name:Department of Life Sciences Core Facilities, Weizmann Institute of Science, Rehovot, Israel
name:Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel
name:Tissue Typing and Immunogenetics Unit, Hadassah Medical Center, Jerusalem, Israel
name:Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel
name:Department of Chemical Research Support, Weizmann Institute of Science, Rehovot, Israel
name:Department of Chemical Research Support, Weizmann Institute of Science, Rehovot, Israel
name:Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel
name:Cancer Data Science Laboratory (CDSL), National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, USA
name:Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel
name:Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel
name:Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel
name:Department of Physics of Complex Systems, Weizmann Institute of Science, Rehovot, Israel
name:The Ruth and Bruce Rappaport Faculty of Medicine, Technion â Israel Institute of Technology, Haifa, Israel
name:Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, USA
name:Cancer Data Science Laboratory (CDSL), National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, USA
name:Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, USA
name:Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, USA
name:Department of Veterinary Pathobiology, Texas A&M University, Houston, USA
name:Department of Infectious Diseases, MD Anderson Cancer Center, Houston, USA
name:Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, USA
name:Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, USA
name:Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, USA
name:Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, USA
name:Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel
name:Department of Veterinary Resources, Weizmann Institute of Science, Rehovot, Israel
name:Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel
name:Department of Computer Science and Applied Mathematics, Weizmann Institute of Science, Rehovot, Israel
name:Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel
name:Department of Computer Science and Applied Mathematics, Weizmann Institute of Science, Rehovot, Israel
name:Sharett Institute of Oncology, Hadassah Hebrew University Medical Center, Jerusalem, Israel
name:Department of Biology, Technion â Israel Institute of Technology, Haifa, Israel
name:The de Botton Institute for Protein Profiling, The Nancy and Stephen Grand Israel National Center for Personalized Medicine, Weizmann Institute of Science, Rehovot, Israel
name:Wellcome Sanger Institute, Cambridge, UK
name:Wellcome Sanger Institute, Cambridge, UK
name:Faculty of Medicine, University of Zurich Hospital, University of Zurich, Zurich, Switzerland
name:The Ella Lemelbaum Institute for Immuno Oncology and Melanoma, Chaim Sheba Medical Center, Tel Hashomer, Israel
name:Department of Clinical Microbiology and Immunology, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
name:The Ella Lemelbaum Institute for Immuno Oncology and Melanoma, Chaim Sheba Medical Center, Tel Hashomer, Israel
name:Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
name:Department of Life Sciences Core Facilities, Weizmann Institute of Science, Rehovot, Israel
name:Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel
name:Department of Computer Science and Applied Mathematics, Weizmann Institute of Science, Rehovot, Israel
name:The Ruth and Bruce Rappaport Faculty of Medicine, Technion â Israel Institute of Technology, Haifa, Israel
name:MaRS Centre, Canadian Institute for Advanced Research (CIFAR) Azrieli Global Scholar, Toronto, Canada
name:Cancer Data Science Laboratory (CDSL), National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, USA
name:Division of Molecular Oncology and Immunology, The Netherlands Cancer Institute, Amsterdam, The Netherlands
name:Sanford Burnham Prebys Medical Discovery Institute, La Jolla, USA
name:Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, USA
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name:Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel
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