journal contribution
posted on 2023-04-04, 01:00 authored by Kerstin Wennhold, Martin Thelen, Jonas Lehmann, Simon Schran, Ella Preugszat, Maria Garcia-Marquez, Axel Lechner, Alexander Shimabukuro-Vornhagen, Meryem S. Ercanoglu, Florian Klein, Fabinshy Thangarajah, Sebastian Eidt, Heike Löser, Christiane Bruns, Alexander Quaas, Michael von Bergwelt-Baildon, Hans A. Schlößer Detailed list of used antibodies
Funding
German Cancer Aid
Center for Molecular Medicine Cologne
German Research Foundation
European Union Regional Fund for Development
History
ARTICLE 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 downregulation 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. BAPCs 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.
