Using 16S rRNA profiling, Kalaora et al. identified 41 bacterial species colonizing 17 melanoma metastases from nine patients; seven species were more abundant in the melanomas than in paired blood samples. HLA immunopeptidomics identified 248 HLA-I- and 35 HLA-II-associated bacterial-derived peptides shared by metastases within a patient or between patients. Peptides binding cognate HLA-I were presented by the melanoma cells. Intracellular bacteria entered melanoma cell lines, and bacterial peptides bound HLA-I/II. Melanoma-infiltrating lymphocytes responded to bacterial peptide-pulsed, HLA-matched antigen-presenting cells.
Contributed by Paula Hochman
ABSTRACT: 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.
Author Info: (1) Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel. (2) Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel.
Author Info: (1) Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel. (2) Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel. (3) Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel. (4) Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel. (5) Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel. (6) Department of Biology, Technion - Israel Institute of Technology, Haifa, Israel. (7) Division of Molecular Oncology and Immunology, The Netherlands Cancer Institute, Amsterdam, The Netherlands. (8) Cancer Data Science Laboratory (CDSL), National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, MD, USA. (9) Wellcome Sanger Institute, Cambridge, UK. (10) Department of Mathematics and Computer Science, Open University of Israel, Raanana, Israel. (11) Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel. Department of Computer Science and Applied Mathematics, Weizmann Institute of Science, Rehovot, Israel. (12) Department of Life Sciences Core Facilities, Weizmann Institute of Science, Rehovot, Israel. (13) Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel. (14) Tissue Typing and Immunogenetics Unit, Hadassah Medical Center, Jerusalem, Israel. (15) Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel. (16) Department of Chemical Research Support, Weizmann Institute of Science, Rehovot, Israel. (17) Department of Chemical Research Support, Weizmann Institute of Science, Rehovot, Israel. (18) Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel. (19) Cancer Data Science Laboratory (CDSL), National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, MD, USA. (20) Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel. (21) Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel. (22) Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel. (23) Department of Physics of Complex Systems, Weizmann Institute of Science, Rehovot, Israel. (24) The Ruth and Bruce Rappaport Faculty of Medicine, Technion - Israel Institute of Technology, Haifa, Israel. (25) Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. (26) Cancer Data Science Laboratory (CDSL), National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, MD, USA. (27) Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. (28) Department of Veterinary Pathobiology, Texas A&M University, Houston, TX, USA. (29) Department of Infectious Diseases, MD Anderson Cancer Center, Houston, TX, USA. (30) Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. (31) Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. (32) Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. (33) Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel. (34) Department of Veterinary Resources, Weizmann Institute of Science, Rehovot, Israel. (35) Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel. Department of Computer Science and Applied Mathematics, Weizmann Institute of Science, Rehovot, Israel. (36) Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel. Department of Computer Science and Applied Mathematics, Weizmann Institute of Science, Rehovot, Israel. (37) Sharett Institute of Oncology, Hadassah Hebrew University Medical Center, Jerusalem, Israel. (38) Department of Biology, Technion - Israel Institute of Technology, Haifa, Israel. (39) The de Botton Institute for Protein Profiling, The Nancy and Stephen Grand Israel National Center for Personalized Medicine, Weizmann Institute of Science, Rehovot, Israel. (40) Wellcome Sanger Institute, Cambridge, UK. (41) Wellcome Sanger Institute, Cambridge, UK. (42) Faculty of Medicine, University of Zurich Hospital, University of Zurich, Zurich, Switzerland. (43) The Ella Lemelbaum Institute for Immuno Oncology and Melanoma, Chaim Sheba Medical Center, Tel Hashomer, Israel. Department of Clinical Microbiology and Immunology, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel. (44) The Ella Lemelbaum Institute for Immuno Oncology and Melanoma, Chaim Sheba Medical Center, Tel Hashomer, Israel. Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel. (45) Department of Life Sciences Core Facilities, Weizmann Institute of Science, Rehovot, Israel. (46) Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel. Department of Computer Science and Applied Mathematics, Weizmann Institute of Science, Rehovot, Israel. (47) The Ruth and Bruce Rappaport Faculty of Medicine, Technion - Israel Institute of Technology, Haifa, Israel. MaRS Centre, Canadian Institute for Advanced Research (CIFAR) Azrieli Global Scholar, Toronto, Ontario, Canada. (48) Cancer Data Science Laboratory (CDSL), National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, MD, USA. (49) Division of Molecular Oncology and Immunology, The Netherlands Cancer Institute, Amsterdam, The Netherlands. (50) Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, USA. (51) Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. (52) Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel. (53) Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel. yardena.samuels@weizmann.ac.il.
