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 LUMINEXTM 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.
journal_name
Oncoimmunologyjournal_title
Oncoimmunologyauthors
Schlößer HA,Thelen M,Lechner A,Wennhold K,Garcia-Marquez MA,Rothschild SI,Staib E,Zander T,Beutner D,Gathof B,Gilles R,Cukuroglu E,Göke J,Shimabukuro-Vornhagen A,Drebber U,Quaas A,Bruns CJ,Hölscher AH,Von Bergwelt-Baidoi
10.1080/2162402X.2018.1512458subject
Has Abstractpub_date
2018-11-02 00:00:00pages
e1512458issue
1eissn
2162-4011issn
2162-402Xpii
1512458journal_volume
8pub_type
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