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

$('.header-date').hide();$('#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.