Oncotarget

Clinical Research Papers:

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

Alexander Shimabukuro-Vornhagen, Hans A. Schlößer _, Luise Gryschok, Joke Malcher, Kerstin Wennhold, Maria Garcia-Marquez, Till Herbold, Laura S. Neuhaus, Hans J. Becker, Anne Fiedler, Pascal Scherwitz, Thomas Koslowsky, Roland Hake, Dirk L. Stippel, Arnulf H. Hoelscher, Sebastian Eidt, Michael Hallek, Sebastian Theurich and Michael S. von Bergwelt-Baildon

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Oncotarget. 2014; 5:4651-4664. https://doi.org/10.18632/oncotarget.1701

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Abstract

Alexander Shimabukuro-Vornhagen1,2,*, Hans A. Schlößer1,3,*, Luise Gryschok1, Joke Malcher1, Kerstin Wennhold1, Maria Garcia-Marquez1, Till Herbold1,3, Laura S. Neuhaus1, Hans J. Becker1, Anne Fiedler1, Pascal Scherwitz4, Thomas Koslowsky5, Roland Hake6, Dirk L. Stippel3, Arnulf H. Hölscher3, Sebastian Eidt6, Michael Hallek2, Sebastian Theurich1,2, Michael S. von Bergwelt-Baildon1,2

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.


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