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Characterization of tumor-associated B-cell subsets in patients with colorectal cancer

2014; Impact Journals LLC; Volume: 5; Issue: 13 Linguagem: Inglês

10.18632/oncotarget.1701

1949-2553

Alexander Shimabukuro‐Vornhagen, Hans Schlößer, Luise Gryschok, Joke Malcher, Kerstin Wennhold, María A. García-Márquez, Till Herbold, L. Neuhaus, H. Becker, Anne Fiedler, Pascal Scherwitz, Thomas C. Koslowsky, Roland Hake, Dirk L. Stippel, Arnulf H. Hölscher, Sebastian Eidt, Michael Hallek, Sebastian Theurich, Michael S. von Bergwelt‐Baildon,

Immune Cell Function and Interaction

$('.header-date').hide();$('#titleAuthors').hide(); $('#abstractHeader').hide(); Alexander Shimabukuro-Vornhagen 1 , 2 , * , Hans A. Schlößer 1 , 3 , * , Luise Gryschok 1 , Joke Malcher 1 , Kerstin Wennhold 1 , Maria Garcia-Marquez 1 , Till Herbold 1 , 3 , Laura S. Neuhaus 1 , Hans J. Becker 1 , Anne Fiedler 1 , Pascal Scherwitz 4 , Thomas Koslowsky 5 , Roland Hake 6 , Dirk L. Stippel 3 , Arnulf H. Hölscher 3 , Sebastian Eidt 6 , Michael Hallek 2 , Sebastian Theurich 1 , 2 , Michael S. von Bergwelt-Baildon 1 , 2 1 Cologne Interventional Immunology, University of Cologne, Germany. 2 Department I of Internal Medicine, University of Cologne, Cologne, Germany. 3 Department of General, Visceral and Cancer Surgery, University of Cologne, Germany. 4 Department of Surgery, Marien Hospital, Brühl, Germany. 5 Department of Surgery, St. Elisabeth Hospital, Cologne, Germany. 6 Institute of Pathology, St. Elisabeth Hospital, Cologne, Germany. * This authors contributed equally to this work. Correspondence to: Michael S. von Bergwelt-Baildon, e-mail: michael.von-bergwelt-baildon@uk-koeln.de Received: December 14, 2013 Accepted: April 28, 2014 Published: May 09, 2014 ABSTRACT Purpose: A precise understanding of the mechanisms by which human immune cell subsets affect tumor biology will be critical for successful treatment of cancer using immunotherapeutic approaches. Recent evidence suggests that B cells can both promote and inhibit the development and progression of tumors. The aim of this study was to characterize the composition of the B-cell infiltrates in colorectal cancers (CRC) in order to gain further insight into the role of B cells in CRC. Experimental Design: In this study we characterized B-cell subsets in primary tumors (n=38), metastases (n=6) and blood (n=46) of 51 patients with a diagnosis of CRC and blood of 10 healthy controls. B-cell subsets were analyzed by flow cytometry or immunohistochemistry. Results: Peripheral blood of CRC patients contained a higher percentage of memory B cells than that of age-matched healthy controls. Furthermore, the percentage of B cells within tumors was higher than that in the peripheral blood of CRC patients while metastases were typically devoid of tumor-infiltrating B cells. Tumor-associated B cells were enriched for activated and terminally differentiated B cells. Relevant proportions of regulatory B cells could only be detected in advanced cancer and metastases. Conclusion: B cells constitute a significant proportion of the immune infiltrate in CRC. The B-cell infiltrate of primary CRC is characterized by an accumulation of terminally differentiated memory B cells or plasma cells suggestive of a specific immune response against the tumor. However advanced tumors and metastases are also infiltrated by a considerable number of regulatory B cells.