title: Impaired migration of IgA-secreting cells to colon adenocarcinomas.
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(+)CD38(high)IgA(+) 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.
authors.affiliation: Department of Microbiology and Immunology, Institute of Biomedicine, The Sahlgrenska Academy at University of Gothenburg, Box 435, 405 30 Göteborg, Sweden.
authors.forename: Rangarajan V
authors.initials: RV
authors.lastname: Muthuswamy
authors.forename: Patrik
authors.initials: P
authors.lastname: Sundström
authors.forename: Lars
authors.initials: L
authors.lastname: Börjesson
authors.forename: Bengt
authors.initials: B
authors.lastname: Gustavsson
authors.forename: Marianne
authors.initials: M
authors.lastname: Quiding-Järbrink
mesh_terms: D000230:Adenocarcinoma / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D000368:Aged; D000369:Aged, 80 and over; D018941:Antigens, CD19 / Q000276:immunology / Q000378:metabolism; D019742:Chemokines, CC / Q000276:immunology / Q000378:metabolism; D002634:Chemotaxis, Leukocyte / Q000276:immunology*; D003110:Colonic Neoplasms / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D007071:Immunoglobulin A, Secretory / Q000096:biosynthesis*; D016130:Immunophenotyping; D007413:Intestinal Mucosa / Q000276:immunology; D016131:Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D010950:Plasma Cells / Q000276:immunology* / Q000378:metabolism; D054447:Receptors, CCR10 / Q000378:metabolism
chemical_list: D018941:Antigens, CD19; C414047:CCL28 protein, human; D019742:Chemokines, CC; D007071:Immunoglobulin A, Secretory; D054447:Receptors, CCR10