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B cells in tumor draining lymph nodes act as efficient antigen presenting cells in cancer patients
  1. A Ali Zirakzadeh1,
  2. David Krantz1,
  3. Malin Winerdal1,
  4. Christian Lundgren1,
  5. Ciputra Adijaya Hartana1,
  6. Emma Ahlén Bergman1,
  7. Johan Hansson2,
  8. Benny Holmström3,
  9. Alexander Sidiki4,
  10. Janos Vasko5,
  11. Markus Johansson6,
  12. Per Marits1,
  13. Amir Sherif7 and
  14. Ola Winqvist1
  1. Aff1 grid.4714.60000000419370626Karolinska Institutet Stockholm Sweden
  2. Aff2 grid.8993.b0000000419369457Centre for Research and Development, Faculty of MedicineUppsala University Uppsala Sweden
  3. Aff3 grid.412354.50000000123513333Department of UrologyUppsala University Hospital Uppsala Sweden
  4. Aff4 Department of UrologyLänssjukhuset Ryhov Jönköping, Jönköping Sweden
  5. Aff5 grid.12650.300000000110343451Department of Medical BiosciencesPathology Umeå University Umeå Sweden
  6. Aff6 grid.416729.f0000000406240320Departemnt of UrologySundsvall Hospital Sundsvall Sweden
  7. Aff7 grid.12650.300000000110343451Department of Surgical and Perioperative Sciences, Urology and AndrologyUmeå University Umeå Sweden

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Meeting abstracts


Overall Survival of patients with muscle invasive urothelial bladder cancer MIBC remains around 50% (5 years), albeit some improvements by combining neoadjuvant chemotherapy with radical surgery. Our previous work has demonstrated that in vitro expansions of sentinel node-acquired autologous tumor specific CD4+ T cells are promising for adoptive immunotherapy [1]. In order for naive T helper cells to become activated, they need effective APCs, presenting tumor antigens. In another study, we observed that B cells in cancer patients were tumor antigen experienced and from their phenotypes we suggested a CD4+ T cell dependent anti-tumoral response [2]. In this study, we report a flow cytometric investigation of tumor draining lymph node (sentinel node) derived B cell activation by autologous tumor extract in patients with MIBC.


Sentinel nodes (SNs) from 28 patients with MIBC were detected by a Geiger meter at cystectomy after peritumoral injection with radioactive isotope. Lymphocytes were isolated from freshly received SNs where they were stimulated with autologous tumor extract in a sterile environment. After cultivation for 7 days, the cells were analyzed by multi-color flow cytometry using FASCIA (Flow cytometric Assay of Specific Cell-mediated Immune response in Activated whole blood).


Patients displayed an increased B cell activation in SNs after stimulation with autologous tumor extract compared to when SN acquired lymphocytes were stimulated with autologous extract of macroscopically non-malignant bladder. CD4+ T cells from SNs were activated and formed blasts after co-culture with SN acquired B cells in the presence of tumor antigen. However, CD4+ T cells were not activated and did not blast when co-cultured with B cells incubated with HLA-DR-blocking antibodies. This indicates antigen presenting ability of SN acquired B cells.


We demonstrate sentinel node acquired B lymphocytes can be activated in culture upon stimulation with autologous tumor extract but not with extract of non-malignant epithelium of the bladder, after 7 days. Lower number of sentinel node acquired CD4+ T cells cultured with HLA-DR blocked CD19+ cells in presence of tumor antigen, indicate functional antigen presenting ability of B cells in sentinel nodes. The role of B cells as APCs in human T cell anti-tumoral response should be further explored, as well as their usefulness in adoptive immunotherapy.


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