Perioperative changes in peripheral regulatory B cells of patients with esophageal cancer

Shi,Jiazhen; Li,Shibao; Zhou,Yan; Wang,Lixin; Wen,Jiangtao; Wang,Yonghong; Kang,Zhihua

doi:10.3892/mmr.2014.2347

Perioperative changes in peripheral regulatory B cells of patients with esophageal cancer

Authors:
- Jiazhen Shi
- Shibao Li
- Yan Zhou
- Lixin Wang
- Jiangtao Wen
- Yonghong Wang
- Zhihua Kang
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Affiliations: Department of Laboratory Medicine, Lianyungang Hospital Affiliated to Bengbu Medical College, Lianyungang, Jiangsu 222006, P.R. China, Department of Microbiology and Immunology, Medical School of Southeast University, Nanjing, Jiangsu 210029, P.R. China, Department of Cardiothoracic Surgery, Lianyungang Hospital Affiliated to Bengbu Medical College, Lianyungang, Jiangsu 222006, P.R. China, Department of Laboratory Medicine, Huashan Hospital, Shanghai Medical School, Fudan University, Shanghai 200040, P.R. China
Published online on: June 19, 2014 https://doi.org/10.3892/mmr.2014.2347
Pages: 1525-1530

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Abstract

Current treatments for esophageal cancer (EC) rely on tumor eradication by surgery or chemoradiotherapy. However, such treatments do not account for the assessment and adjustment of the immune status of the patients. Regulatory B cells (Bregs) have been confirmed as a negative regulatory subtype in B‑cell populations. However, to the best of our knowledge, there have been no direct studies on Bregs in patients with EC. The present study enrolled sixty patients with EC and sixty healthy donors to detect the presence of Bregs in peripheral blood and to determine their clinical significance. The percentage of peripheral Bregs was measured using flow cytometry with fluorescence‑labeled antibodies against cluster of differentiation (CD) 5, CD19, interleukin (IL)‑10, forkhead box protein 3 (Foxp3) and transforming growth factor‑β1 (TGF‑β1) prior to and following radical surgery. The level of circulating Bregs in patients with EC was observed to be significantly higher than that in the healthy donors. However, this level was observed to decrease following surgery. The percentage of circulating TGF‑β‑producing Bregs and Foxp3‑expressing Bregs in patients with EC also decreased following surgery. By contrast, the percentage of peripheral IL‑10‑producing Bregs (B10s) significantly increased in patients with advanced EC following surgery. These findings suggest that Bregs have a negative immunoregulatory role in the development and progression of EC. Furthermore, postoperative combination therapies against Bregs, particularly B10s, may improve the outcome of patients with EC following resection.

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1	Kamangar F, Dores GM and Andeson WF: Patterns of cancer incidence, mortality, and prevalence across five continents: defining priorities to reduce cancer disparities in different geographic regions of the world. J Clin Oncol. 24:2137–2150. 2006. View Article : Google Scholar
2	Ferlay J, Shin HR, Bray F, Forman D, Mathers C and Parkin DM: Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer. 127:2893–2917. 2010. View Article : Google Scholar : PubMed/NCBI
3	Enzinger PC and Mayer RJ: Esophageal Cancer. N Engl J Med. 349:2241–2252. 2003. View Article : Google Scholar : PubMed/NCBI
4	Watanabe R, Ishiura N, Nakashima H, Kuwano Y, Okochi H, Tamaki K, Sato S, Tedder TF and Fujimoto M: Regulatory B cells (B10 cells) have a suppressive role in murine lupus: CD19 and B10 cell deficiency exacerbates systemic autoimmunity. J Immunol. 184:4801–4809. 2010. View Article : Google Scholar
5	Olkhanud PB, Damdinsuren B, Bodogai M, Gress RE, Sen R, Wejksza K, Malchinkhuu E, Wersto RP and Biragyn A: Tumor-evoked regulatory B cells promote breast cancer metastasis by converting resting CD4⁺ T cells to T-regulatory cells. Cancer Res. 71:3505–3515. 2011. View Article : Google Scholar : PubMed/NCBI
6	Schioppa T, Moore R, Thompson RG, Rosser EC, Kulbe H, Nedospasov S, Mauri C, Coussens LM and Balkwill FR: B regulatory cells and the tumor promoting actions of TNF-α during squamous carcinogenesis. Proc Natl Acad Sci USA. 108:10662–10667. 2011.PubMed/NCBI
7	Huang C and Fu ZX: Localization of IL-17⁺Foxp3⁺ T cells in esophageal cancer. Immunol Invest. 40:400–412. 2011.
8	Mauri C and Bosma A: Immune regulatory function of B cells. Annu Rev Immunol. 30:221–241. 2012. View Article : Google Scholar : PubMed/NCBI
9	Lund FE and Randall TD: Effector and regulatory B cells: modulators of CD4⁺ T cell immunity. Nat Rev Immunol. 10:236–247. 2010. View Article : Google Scholar : PubMed/NCBI
10	Noh G and Lee JH: Regulatory B cells and allergic diseases. Allergy Asthma Immunol Res. 3:168–177. 2011. View Article : Google Scholar : PubMed/NCBI
11	Watanabe R, Fujimoto M, Ishiura N, Kuwano Y, Nakashima H, Yazawa N, Okochi H, Sato S, Tedder TF and Tamaki K: CD19 expression in B cells is important for suppression of contact hypersensitivity. Am J Pathol. 171:560–570. 2007. View Article : Google Scholar : PubMed/NCBI
12	Yanaba K, Bouaziz JD, Haas KM, Poe JC, Fujimoto M and Tedder TF: A regulatory B cell subset with a unique CD1dhiCD5⁺ phenotype controls T cell-dependent inflammatory responses. Immunity. 28:639–650. 2008. View Article : Google Scholar : PubMed/NCBI
13	Matsushita T, Yanaba K, Bouaziz JD, Fujimoto M and Tedder TF: Regulatory B cells inhibit EAE initiation in mice while other B cells promote disease progression. J Clin Invest. 118:3420–3430. 2008.PubMed/NCBI
14	Fillatreau S, Sweenie CH, McGeachy MJ, Gray D and Anderton SM: B cells regulate autoimmunity by provision of IL-10. Nat Immunol. 3:944–950. 2002. View Article : Google Scholar : PubMed/NCBI
15	Mizoguchi A, Mizoguchi E, Takedatsu H, Blumberg RS and Bhan AK: Chronic intestinal inflammatory condition generates IL-10-producing regulatory B cell subset characterized by CD1d upregulation. Immunity. 16:219–230. 2002. View Article : Google Scholar : PubMed/NCBI
16	Fillatreau S, Gray D and Anderton SM: Not always the bad guys: B cells as regulators of autoimmune pathology. Nat Rev Immunol. 8:391–397. 2008. View Article : Google Scholar : PubMed/NCBI
17	DiLillo DJ, Matsushita T and Tedder TF: B10 cells and regulatory B cells balance immune responses during inflammation, autoimmunity, and cancer. Ann NY Acad Sci. 1183:38–57. 2010. View Article : Google Scholar : PubMed/NCBI
18	Mauri C and Ehrenstein MR: The ‘short’ history of regulatory B cells. Trends Immunol. 29:34–40. 2008.
19	Mizoguchi A and Bhan AK: A case for regulatory B cells. J Immunol. 176:705–710. 2006. View Article : Google Scholar
20	Mosser D and Zhang X: Interleukin-10: new perspectives on an old cytokine. Immunol Rev. 226:205–218. 2008. View Article : Google Scholar : PubMed/NCBI
21	Edge S, Byrd DR, Compton CC, Fritz AG, Greene FL and Trotti A: AJCC Cancer Staging Manual. Seventh edition. Springer; New York, NY: 2010
22	Inoue S, Leitner WW, Golding B and Scott D: Inhibitory effects of B cells on antitumor immunity. Cancer Res. 66:7741–7747. 2006. View Article : Google Scholar : PubMed/NCBI
23	Chen T, Song D, Min Z, et al: Perioperative dynamic alterations in peripheral regulatory T and B cells in patients with hepatocellular carcinoma. J Transl Med. 10:142012. View Article : Google Scholar : PubMed/NCBI
24	Im SH, Hueber A, Monticelli S, Kang KH and Rao A: Chromatin-level regulation of the IL10 gene in T cells. J Biol Chem. 279:46818–46825. 2004. View Article : Google Scholar : PubMed/NCBI
25	Lee JH, Noh J, Noh G, Choi WS and Lee SS: IL-10 is predominantly produced by the CD19(low)CD5(+) regulatory B cell subpopulation: characterization of CD19(high) and CD19(low) subpopulations of CD5(+) B cells. Yonsei Med J. 52:851–855. 2011. View Article : Google Scholar : PubMed/NCBI
26	Lee JH, Noh J, Noh G, Kim HS, Mun SH, Choi WS, Cho S and Lee S: Allergen-specific B cell subset responses in cow’s milk allergy of late eczematous reactions in atopic dermatitis. Cell Immunol. 262:44–51. 2010.
27	Itoh S and Itoh F: Implication of TGF-β as a survival factor during tumour development. J Biochem. 151:559–562. 2012.
28	Hoshino Y, Katsuno Y, Ehata S and Miyazono K: Autocrine TGF-β protects breast cancer cells from apoptosis through reduction of BH3-only protein, Bim. J Biochem. 149:55–65. 2011.
29	Edlund S, Bu S, Schuster N, Aspenström P, Heuchel R, Heldin NE, ten Dijke P, Heldin CH and Landström M: Transforming growth factor-beta1 (TGF-beta)-induced apoptosis of prostate cancer cells involves Smad7-dependent activation of p38 by TGF-beta-activated kinase 1 and mitogen-activated protein kinase kinase 3. Mol Biol Cell. 14:529–544. 2003. View Article : Google Scholar
30	Miller AV, Alvarez SE, Spiegel S and Lebman DA: Sphingosine kinases and sphingosine-1-phosphate are critical for transforming growth factor beta-induced extracellular signal-regulated kinase 1 and 2 activation and promotion of migration and invasion of esophageal cancer cells. Mol Cell Biol. 28:4142–4151. 2008. View Article : Google Scholar
31	Tian J, Zekzer D, Hanssen L, Lu Y, Olcott A and Kaufman DL: Lipopolysaccharide-activated B cells down-regulate Th1 immunity and prevent autoimmune diabetes in nonobese diabetic mice. J Immunol. 167:1081–1089. 2001. View Article : Google Scholar : PubMed/NCBI
32	Lee JH, Noh J, Noh G, Choi WS, Cho S and Lee SS: Allergen-specific transforming growth factor-β-producing CD19⁺CD5⁺ regulatory B-cell (Br3) responses in human late eczematous allergic reactions to cow’s milk. J Interferon Cytokine Res. 31:441–449. 2011.
33	Hori S, Nomura T and Sakaguchi S: Control of regulatory T cell development by the transcription factor Foxp3. Science. 299:1057–1061. 2003. View Article : Google Scholar : PubMed/NCBI
34	Wang G, Liu G, Liu Y, Li X and Su Z: FOXP3 Expression in esophageal cancer cells is associated with poor prognosis in esophageal cancer. Hepatogastroenterology. 59:2186–2191. 2012.PubMed/NCBI
35	Noh J, Choi WS, Noh G and Lee JH: Presence of Foxp3-expressing CD19(+)CD5(+) B Cells in human peripheral blood mononuclear cells: Human CD19(+)CD5(+)Foxp3(+) regulatory B cell (Breg). Immune Netw. 10:247–249. 2010. View Article : Google Scholar : PubMed/NCBI
36	Baumgartner C, Osl M, Netzer M and Baumgartner D: Bioinformatic-driven search for metabolic biomarkers in disease. J Clin Bioinforma. 1:22011. View Article : Google Scholar : PubMed/NCBI
37	Wang X and Liotta L: Clinical bioinformatics: a new emerging science. J Clin Bioinforma. 1:12011. View Article : Google Scholar : PubMed/NCBI