Immunogenetic Profiling for Gastric Cancers Identifies Sulfated Glycosaminoglycans as Major and Functional B Cell Antigens in Human Malignancies
Summary: Recent successes in tumor immunotherapies have highlighted the importance of tumor immunity. However, most of the work conducted to date has been on T cell immunity, while the role of B cell immunity in cancer remains more elusive. In this study, immunogenetic repertoire profiling for tumor...
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Elsevier
2017-08-01
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| Series: | Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124717309695 |
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doaj-f445a5c3d6c74a48abcedc9724653d6b2020-11-25T01:51:03ZengElsevierCell Reports2211-12472017-08-0120510731087Immunogenetic Profiling for Gastric Cancers Identifies Sulfated Glycosaminoglycans as Major and Functional B Cell Antigens in Human MalignanciesHiroto Katoh0Daisuke Komura1Hiroki Konishi2Ryohei Suzuki3Asami Yamamoto4Miwako Kakiuchi5Reiko Sato6Tetsuo Ushiku7Shogo Yamamoto8Kenji Tatsuno9Takashi Oshima10Sachiyo Nomura11Yasuyuki Seto12Masashi Fukayama13Hiroyuki Aburatani14Shumpei Ishikawa15Department of Genomic Pathology, Medical Research Institute, Tokyo Medical and Dental University, 113-8510 Tokyo, JapanDepartment of Genomic Pathology, Medical Research Institute, Tokyo Medical and Dental University, 113-8510 Tokyo, JapanDepartment of Genomic Pathology, Medical Research Institute, Tokyo Medical and Dental University, 113-8510 Tokyo, JapanDepartment of Genomic Pathology, Medical Research Institute, Tokyo Medical and Dental University, 113-8510 Tokyo, JapanDepartment of Genomic Pathology, Medical Research Institute, Tokyo Medical and Dental University, 113-8510 Tokyo, JapanGenome Science Division, Research Center for Advanced Science and Technology, University of Tokyo, 153-0041 Tokyo, JapanDepartment of Genomic Pathology, Medical Research Institute, Tokyo Medical and Dental University, 113-8510 Tokyo, JapanDepartment of Pathology, Graduate School of Medicine, University of Tokyo, 113-0033 Tokyo, JapanGenome Science Division, Research Center for Advanced Science and Technology, University of Tokyo, 153-0041 Tokyo, JapanGenome Science Division, Research Center for Advanced Science and Technology, University of Tokyo, 153-0041 Tokyo, JapanDepartment of Surgery, Yokohama City University, 236-0027 Kanagawa, JapanDepartment of Gastrointestinal Surgery, Graduate School of Medicine, University of Tokyo, 113-0033 Tokyo, JapanDepartment of Gastrointestinal Surgery, Graduate School of Medicine, University of Tokyo, 113-0033 Tokyo, JapanDepartment of Pathology, Graduate School of Medicine, University of Tokyo, 113-0033 Tokyo, JapanGenome Science Division, Research Center for Advanced Science and Technology, University of Tokyo, 153-0041 Tokyo, JapanDepartment of Genomic Pathology, Medical Research Institute, Tokyo Medical and Dental University, 113-8510 Tokyo, Japan; Corresponding authorSummary: Recent successes in tumor immunotherapies have highlighted the importance of tumor immunity. However, most of the work conducted to date has been on T cell immunity, while the role of B cell immunity in cancer remains more elusive. In this study, immunogenetic repertoire profiling for tumor-infiltrating B and T cells in gastric cancers was carried out to help reveal the architecture of B cell immunity in cancer. Humoral immunity in cancer was shown to involve oligoclonal expansions of tumor-specific and private B cell repertoires. We find that B cell repertoires in cancer are shaped by somatic hypermutation (SHM) either with or without positive selection biases, the latter of which tended to be auto-reactive. Importantly, we identified sulfated glycosaminoglycans (GAGs) as major functional B cell antigens among gastric tumors. Furthermore, natural anti-sulfated GAG antibodies discovered in gastric cancer tissues showed robust growth-suppressive functions against a wide variety of human malignancies of various organs. : Katoh et al. profile immunoglobulin repertoires of tumor-infiltrating B cells, identifying sulfated glycosaminoglycan as a major functional B cell antigen in tumors. Repertoire profiling for tumor-infiltrating B cells may pave the way to the development of therapeutic antibodies. Keywords: repertoire sequence, immunogenetics, tumor immunity, tumor-infiltrating B cell, sulfated glycosaminoglycan, therapeutic antibody, gastric cancerhttp://www.sciencedirect.com/science/article/pii/S2211124717309695 |
| collection |
DOAJ |
| language |
English |
| format |
Article |
| sources |
DOAJ |
| author |
Hiroto Katoh Daisuke Komura Hiroki Konishi Ryohei Suzuki Asami Yamamoto Miwako Kakiuchi Reiko Sato Tetsuo Ushiku Shogo Yamamoto Kenji Tatsuno Takashi Oshima Sachiyo Nomura Yasuyuki Seto Masashi Fukayama Hiroyuki Aburatani Shumpei Ishikawa |
| spellingShingle |
Hiroto Katoh Daisuke Komura Hiroki Konishi Ryohei Suzuki Asami Yamamoto Miwako Kakiuchi Reiko Sato Tetsuo Ushiku Shogo Yamamoto Kenji Tatsuno Takashi Oshima Sachiyo Nomura Yasuyuki Seto Masashi Fukayama Hiroyuki Aburatani Shumpei Ishikawa Immunogenetic Profiling for Gastric Cancers Identifies Sulfated Glycosaminoglycans as Major and Functional B Cell Antigens in Human Malignancies Cell Reports |
| author_facet |
Hiroto Katoh Daisuke Komura Hiroki Konishi Ryohei Suzuki Asami Yamamoto Miwako Kakiuchi Reiko Sato Tetsuo Ushiku Shogo Yamamoto Kenji Tatsuno Takashi Oshima Sachiyo Nomura Yasuyuki Seto Masashi Fukayama Hiroyuki Aburatani Shumpei Ishikawa |
| author_sort |
Hiroto Katoh |
| title |
Immunogenetic Profiling for Gastric Cancers Identifies Sulfated Glycosaminoglycans as Major and Functional B Cell Antigens in Human Malignancies |
| title_short |
Immunogenetic Profiling for Gastric Cancers Identifies Sulfated Glycosaminoglycans as Major and Functional B Cell Antigens in Human Malignancies |
| title_full |
Immunogenetic Profiling for Gastric Cancers Identifies Sulfated Glycosaminoglycans as Major and Functional B Cell Antigens in Human Malignancies |
| title_fullStr |
Immunogenetic Profiling for Gastric Cancers Identifies Sulfated Glycosaminoglycans as Major and Functional B Cell Antigens in Human Malignancies |
| title_full_unstemmed |
Immunogenetic Profiling for Gastric Cancers Identifies Sulfated Glycosaminoglycans as Major and Functional B Cell Antigens in Human Malignancies |
| title_sort |
immunogenetic profiling for gastric cancers identifies sulfated glycosaminoglycans as major and functional b cell antigens in human malignancies |
| publisher |
Elsevier |
| series |
Cell Reports |
| issn |
2211-1247 |
| publishDate |
2017-08-01 |
| description |
Summary: Recent successes in tumor immunotherapies have highlighted the importance of tumor immunity. However, most of the work conducted to date has been on T cell immunity, while the role of B cell immunity in cancer remains more elusive. In this study, immunogenetic repertoire profiling for tumor-infiltrating B and T cells in gastric cancers was carried out to help reveal the architecture of B cell immunity in cancer. Humoral immunity in cancer was shown to involve oligoclonal expansions of tumor-specific and private B cell repertoires. We find that B cell repertoires in cancer are shaped by somatic hypermutation (SHM) either with or without positive selection biases, the latter of which tended to be auto-reactive. Importantly, we identified sulfated glycosaminoglycans (GAGs) as major functional B cell antigens among gastric tumors. Furthermore, natural anti-sulfated GAG antibodies discovered in gastric cancer tissues showed robust growth-suppressive functions against a wide variety of human malignancies of various organs. : Katoh et al. profile immunoglobulin repertoires of tumor-infiltrating B cells, identifying sulfated glycosaminoglycan as a major functional B cell antigen in tumors. Repertoire profiling for tumor-infiltrating B cells may pave the way to the development of therapeutic antibodies. Keywords: repertoire sequence, immunogenetics, tumor immunity, tumor-infiltrating B cell, sulfated glycosaminoglycan, therapeutic antibody, gastric cancer |
| url |
http://www.sciencedirect.com/science/article/pii/S2211124717309695 |
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