Wennhold, Kerstin, Thelen, Martin ORCID: 0000-0002-2785-9726, Lehmann, Jonas, Schran, Simon, Preugszat, Ella, Garcia-Marquez, Maria, Lechner, Axel, Shimabukuro-Vornhagen, Alexander, Ercanoglu, Meryem S., Klein, Florian, Thangarajah, Fabinshy, Eidt, Sebastian, Loeser, Heike, Bruns, Christiane, Quaas, Alexander, von Bergwelt-Baildon, Michael and Schloesser, Hans A. (2021). CD86(+) Antigen-Presenting B Cells Are Increased in Cancer, Localize in Tertiary Lymphoid Structures, and Induce Specific T-cell Responses. Cancer Immunol. Res., 9 (9). S. 1098 - 1109. PHILADELPHIA: AMER ASSOC CANCER RESEARCH. ISSN 2326-6074

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Abstract

The role of B cells in antitumor immunity and their impact on emerging immunotherapies is increasingly gaining attention. B-cell effector functions include not only secretion of antibodies, but also presentation of antigens to T cells. A physiologic B-cell subset with immunostimulatory properties was described in humans, defined by a high expression of CD86 and down regulation of CD21. We used multicolor flow cytometry and IHC to elucidate abundance and spatial distribution of these antigen-presenting B cells (BAPC) in blood (peripheral blood mononuclear cells, PBMC) and tumor samples of 237 patients with cancer. Antigen-specific T-cell responses to cancer testis antigens were determined using tetramer staining and sorted BAPCs in FluoroSpot assays for selected patients. We found that BAPCs were increased in the tumor microenvironment of 9 of 10 analyzed cancer types with site-specific variation. BAPCs were not increased in renal cell carcinoma, whereas we found a systemic increase with elevated fractions in tumor-infiltrating lymphocytes (TIL) and PBMCs of patients with colorectal cancer and gastroesophageal adenocarcinoma. BA PCs were localized in lymphoid follicles of tertiary lymphoid structures (TLS) and were enriched in tumors with increased numbers of TLSs. BAPCs isolated from tumor-draining lymph nodes of patients with cancer showed increased percentages of tumor antigen-specific B cells and induced responses of autologous T cells in vitro. Our results highlight the relevance of BAPCs as professional antigen-presenting cells in tumor immunity and provide a mechanistic rationale for the observed correlation of B-cell abundance and response to immune checkpoint inhibition.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Wennhold, KerstinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Thelen, MartinUNSPECIFIEDorcid.org/0000-0002-2785-9726UNSPECIFIED
Lehmann, JonasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schran, SimonUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Preugszat, EllaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Garcia-Marquez, MariaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lechner, AxelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Shimabukuro-Vornhagen, AlexanderUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ercanoglu, Meryem S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Klein, FlorianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Thangarajah, FabinshyUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Eidt, SebastianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Loeser, HeikeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bruns, ChristianeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Quaas, AlexanderUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
von Bergwelt-Baildon, MichaelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schloesser, Hans A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-590106
DOI: 10.1158/2326-6066.CIR-20-0949
Journal or Publication Title: Cancer Immunol. Res.
Volume: 9
Number: 9
Page Range: S. 1098 - 1109
Date: 2021
Publisher: AMER ASSOC CANCER RESEARCH
Place of Publication: PHILADELPHIA
ISSN: 2326-6074
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
PLASMA-CELLS; PARALLEL DETECTION; PROGNOSTIC IMPACT; TUMOR; IMMUNOTHERAPY; ESOPHAGEAL; SURVIVAL; ANTIBODYMultiple languages
Oncology; ImmunologyMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/59010

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