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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Main Authors: 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
Format: Article
Language:English
Published: Elsevier 2017-08-01
Series:Cell Reports
Online Access:http://www.sciencedirect.com/science/article/pii/S2211124717309695
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Summary: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
ISSN:2211-1247