title: Characterization of tumor-associated B-cell subsets in patients with colorectal cancer.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Cologne Interventional Immunology, University of Cologne, Germany. Department I of Internal Medicine, University of Cologne, Cologne, Germany. This authors contributed equally to this work.
authors.forename: Alexander
authors.initials: A
authors.lastname: Shimabukuro-Vornhagen
authors.affiliation: Cologne Interventional Immunology, University of Cologne, Germany. Department of General, Visceral and Cancer Surgery, University of Cologne, Germany. This authors contributed equally to this work.
authors.forename: Hans A
authors.initials: HA
authors.lastname: Schlößer
authors.affiliation: Cologne Interventional Immunology, University of Cologne, Germany.
authors.forename: Luise
authors.initials: L
authors.lastname: Gryschok
authors.affiliation: Cologne Interventional Immunology, University of Cologne, Germany.
authors.forename: Joke
authors.initials: J
authors.lastname: Malcher
authors.affiliation: Cologne Interventional Immunology, University of Cologne, Germany.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Wennhold
authors.affiliation: Cologne Interventional Immunology, University of Cologne, Germany.
authors.forename: Maria
authors.initials: M
authors.lastname: Garcia-Marquez
authors.affiliation: Cologne Interventional Immunology, University of Cologne, Germany. Department of General, Visceral and Cancer Surgery, University of Cologne, Germany.
authors.forename: Till
authors.initials: T
authors.lastname: Herbold
authors.affiliation: Cologne Interventional Immunology, University of Cologne, Germany.
authors.forename: Laura S
authors.initials: LS
authors.lastname: Neuhaus
authors.affiliation: Cologne Interventional Immunology, University of Cologne, Germany.
authors.forename: Hans J
authors.initials: HJ
authors.lastname: Becker
authors.affiliation: Cologne Interventional Immunology, University of Cologne, Germany.
authors.forename: Anne
authors.initials: A
authors.lastname: Fiedler
authors.affiliation: Department of Surgery, Marien Hospital, Brühl, Germany.
authors.forename: Pascal
authors.initials: P
authors.lastname: Scherwitz
authors.affiliation: Department of Surgery, St. Elisabeth Hospital, Cologne, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Koslowsky
authors.affiliation: Institute of Pathology, St. Elisabeth Hospital, Cologne, Germany.
authors.forename: Roland
authors.initials: R
authors.lastname: Hake
authors.affiliation: Department of General, Visceral and Cancer Surgery, University of Cologne, Germany.
authors.forename: Dirk L
authors.initials: DL
authors.lastname: Stippel
authors.affiliation: Department of General, Visceral and Cancer Surgery, University of Cologne, Germany.
authors.forename: Arnulf H
authors.initials: AH
authors.lastname: Hölscher
authors.affiliation: Institute of Pathology, St. Elisabeth Hospital, Cologne, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Eidt
authors.affiliation: Department I of Internal Medicine, University of Cologne, Cologne, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Hallek
authors.affiliation: Cologne Interventional Immunology, University of Cologne, Germany. Department I of Internal Medicine, University of Cologne, Cologne, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Theurich
authors.affiliation: Cologne Interventional Immunology, University of Cologne, Germany. Department I of Internal Medicine, University of Cologne, Cologne, Germany.
authors.forename: Michael S
authors.initials: MS
authors.lastname: von Bergwelt-Baildon
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000276:immunology / Q000378:metabolism; D016175:B-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000097:blood / Q000276:immunology* / Q000473:pathology; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D007156:Immunologic Memory / Q000276:immunology; D016130:Immunophenotyping; D019394:Ki-67 Antigen / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D010950:Plasma Cells / Q000276:immunology / Q000378:metabolism
chemical_list: D015703:Antigens, CD; D019394:Ki-67 Antigen