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Impaired migration of IgA-secreting cells to colon adenocarcinomas

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Abstract

Local inflammation is a strong risk factor for the development of gastrointestinal adenocarcinomas. Mucosal regulatory T cells and IgA-secreting cells both contribute to reduce inflammatory responses, and their recruitment to tissues is dependent on local production of chemokines. More specifically, IgA-secreting cells are recruited to mucosal tissues by CCL28 signalling through CCR10. Here, we examined the recruitment of IgA-secreting plasma cells to tumor-associated mucosa in patients suffering from colon adenocarcinoma. Flow cytometric analyses of single cell suspensions from tumor-associated and unaffected colon mucosa showed a marked decrease in CD19+CD38highIgA+ plasmablasts in the tumor-associated mucosa, while the total frequencies of B and T cells were similar. This finding was confirmed in ELISPOT assays, demonstrating a 64 % reduction in the frequencies of IgA-secreting cells among cells from the tumor-associated mucosa. The few IgA+ plasmablasts present in the tumor did not express CCR10, and functional migration assays demonstrated that IgA-secreting cells from tumor-associated mucosa did not migrate in response to CCL28. Taken together, our results show an impaired migration of IgA-secreting cells to colon tumors, presumably caused by a decreased production of CCL28 in the tumor. The lack of local IgA antibodies may lead to impaired barrier function and increased bacterial colonization, driving further inflammatory responses and promoting tumor growth.

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Acknowledgments

The authors would like to thank all patients who participated in the study, and Hillevi Björkqvist and Ann-Louise Helminnen for valuable help with collection of clinical samples. The study was supported by grants from the Swedish Research Council, The Swedish Cancer Foundation, The Sahlgrenska University Hospital, Inga-Britt and Arne Lundberg’s Foundation, Professor Nanna Svartz’s Foundation, Ruth and Richard Julin’s Foundation, and the Swedish Medical Association.

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Microbiology and Immunology, Institute of Biomedicine, The Sahlgrenska Academy at University of Gothenburg, Box 435, 405 30, Göteborg, Sweden

    Rangarajan V. Muthuswamy, Patrik Sundström & Marianne Quiding-Järbrink

  2. Department of Surgery, Institute of Medicine, The Sahlgrenska Academy at the University of Gothenburg, Göteborg, Sweden

    Lars Börjesson & Bengt Gustavsson

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  1. Rangarajan V. Muthuswamy
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Correspondence to Marianne Quiding-Järbrink.

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Muthuswamy, R.V., Sundström, P., Börjesson, L. et al. Impaired migration of IgA-secreting cells to colon adenocarcinomas. Cancer Immunol Immunother 62, 989–997 (2013). https://doi.org/10.1007/s00262-013-1410-1

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