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B cells in tumor draining lymph nodes act as efficient antigen presenting cells in cancer patients
Journal for ImmunoTherapy of Cancer volume 3, Article number: P65 (2015)
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 . 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 . 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.
Karlsson Marits, Dahl Dagöö, Enerbäck Thörn, Dagoo T, Enerback S, Thorn M, et al: Study of Sentinel-Node-Based Adoptive Immunotherapy in Advanced Colorectal Cancer. Ann Surg Oncol. 2010, 17 (7): 1747-1757.
Zirakzadeh AA, Marits P, Sherif A, Winqvist O: Multiplex B cell characterization in Blood, lymph nodes and tumors from patinets with malignancies. J Immunol. 2013, 190 (11): 5847-5855.
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Zirakzadeh, A.A., Krantz, D., Winerdal, M. et al. B cells in tumor draining lymph nodes act as efficient antigen presenting cells in cancer patients. j. immunotherapy cancer 3, P65 (2015). https://doi.org/10.1186/2051-1426-3-S2-P65
- Sentinel Node
- Tumor Antigen
- Adoptive Immunotherapy
- Urothelial Bladder
- Flow Cytometric Assay