Schloesser, Hans A., Thelen, Martin ORCID: 0000-0002-2785-9726, Lechner, Axel, Wennhold, Kerstin, Garcia-Marquez, Maria A., Rothschild, Sacha I., Staib, Elena, Zander, Thomas, Beutner, Dirk, Gathof, Birgit, Gilles, Ramona, Cukuroglu, Engin, Goke, Jonathan ORCID: 0000-0002-0825-4991, Shimabukuro-Vornhagen, Alexander, Drebber, Uta, Quaas, Alexander, Bruns, Christiane J., Hoelscher, Arnulf H. and Von Bergwelt-Baildon, Michael S. (2019). B cells in esophago-gastric adenocarcinoma are highly differentiated, organize in tertiary lymphoid structures and produce tumor-specific antibodies. OncoImmunology, 8 (1). PHILADELPHIA: TAYLOR & FRANCIS INC. ISSN 2162-402X

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Abstract

Tumor-infiltrating lymphocytes (TILs) are correlated to prognosis of several kinds of cancer. Most studies focused on T cells, while the role of tumor-associated B cells (TABs) has only recently gained more attention. TABs contain subpopulations with distinct functions, potentially promoting or inhibiting immune responses. This study provides a detailed analysis of TABs in gastro-esophageal adenocarcinoma (EAC). Flow cytometric analyses of single cell suspensions of tumor samples, mucosa, lymph nodes and peripheral blood mononuclear cells (PBMC) of EAC patients and healthy controls revealed a distinct B cell compartment in cancer patients. B cells were increased in tumor samples and subset-analyses of TILs showed increased proportions of differentiated and activated B cells and an enrichment for follicular T helper cells. Confocal microscopy demonstrated that TABs were mainly organized in tertiary lymphoid structures (TLS), which resemble lymphoid follicles in secondary lymphoid organs. A panel of 34 tumor-associated antigens (TAAs) expressed in EAC was identified based on public databases and TCGA data to analyze tumor-specific B cell responses using a LUMINEX (TM) bead assay and flow cytometry. Structural analyses of TLS and the detection of tumor-specific antibodies against one or more TAAs in 48.1% of analyzed serum samples underline presence of anti-tumor B cell responses in EAC. Interestingly, B cells were decreased in tumors with expression of Programmed Death Ligand 1 or impaired HLA-I expression. These data demonstrate that anti-tumor B cell responses are an additional and underestimated aspect of EAC. Our results are of immediate translational relevance to emerging immunotherapies.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Schloesser, Hans A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Thelen, MartinUNSPECIFIEDorcid.org/0000-0002-2785-9726UNSPECIFIED
Lechner, AxelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wennhold, KerstinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Garcia-Marquez, Maria A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rothschild, Sacha I.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Staib, ElenaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Zander, ThomasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Beutner, DirkUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gathof, BirgitUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gilles, RamonaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Cukuroglu, EnginUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Goke, JonathanUNSPECIFIEDorcid.org/0000-0002-0825-4991UNSPECIFIED
Shimabukuro-Vornhagen, AlexanderUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Drebber, UtaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Quaas, AlexanderUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bruns, Christiane J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hoelscher, Arnulf H.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Von Bergwelt-Baildon, Michael S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-140003
DOI: 10.1080/2162402X.2018.1512458
Journal or Publication Title: OncoImmunology
Volume: 8
Number: 1
Date: 2019
Publisher: TAYLOR & FRANCIS INC
Place of Publication: PHILADELPHIA
ISSN: 2162-402X
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
IMMUNE CELLS; T-CELLS; EXPRESSION; ESOPHAGEAL; SENSITIVITY; METASTASIS; LANDSCAPE; DOCETAXEL; BLOODMultiple languages
Oncology; ImmunologyMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/14000

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