Journal
CELL REPORTS
Volume 20, Issue 5, Pages 1073-1087Publisher
CELL PRESS
DOI: 10.1016/j.celrep.2017.07.016
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Funding
- JSPS KAKENHI [26710009]
- AMED Practical Research for Innovative Cancer Control [15ck0106172h0002]
- Mitsubishi Foundation
- Takeda Science Foundation
- AMED Basic Science and Platform Technology Program for Innovative Biological Medicine [17am0301011h0004]
- AMED Project for Cancer Research and Therapeutic Evolution (P-CREATE) [17cm0106514h0002]
- Joint Usage/Research Program of Medical Research Institute, TMDU
- Grants-in-Aid for Scientific Research [26710009] Funding Source: KAKEN
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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.
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