B cells in esophago-gastric adenocarcinoma are highly differentiated, organize in tertiary lymphoid structures and produce tumor-specific antibodies. (2nd January 2019)

• Record Type: Journal Article
• Authors: Schlößer, Hans A.; Thelen, Martin; Lechner, Axel; Wennhold, Kerstin; Garcia-Marquez, Maria A.; Rothschild, Sacha I.; Staib, Elena; Zander, Thomas; Beutner, Dirk; Gathof, Birgit; Gilles, Ramona; Cukuroglu, Engin; Göke, Jonathan; Shimabukuro-Vornhagen, Alexander; Drebber, Uta; Quaas, Alexander; Bruns, Christiane J.; Hölscher, Arnulf H.; Von Bergwelt-Baildon, Michael S.
• Is Part Of: Oncoimmunology. Volume 8:Number 1(2019)
• Publication Date: 2019-01-02
• Subjects: Plasma cells -- tumor associated antigen -- antibody -- esophageal cancer; Tumors -- Immunological aspects -- Periodicals; Neoplasms -- therapy -- Periodicals; Immunotherapy -- Periodicals; 616.994
• DOI: 10.1080/2162402X.2018.1512458
• Languages: English
• ISSNs: 2162-402X

Abstract

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.