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  • Open Access

B cells in tumor draining lymph nodes act as efficient antigen presenting cells in cancer patients

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Journal for ImmunoTherapy of Cancer20153 (Suppl 2) :P65

https://doi.org/10.1186/2051-1426-3-S2-P65

  • Published:

Keywords

  • Sentinel Node
  • Tumor Antigen
  • Adoptive Immunotherapy
  • Urothelial Bladder
  • Flow Cytometric Assay

Introduction

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.

Methods

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).

Results

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.

Conclusions

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.

Authors’ Affiliations

(1)
Karolinska Institutet, Stockholm, Sweden
(2)
Centre for Research and Development, Faculty of Medicine, Uppsala University, Uppsala, Sweden
(3)
Department of Urology, Uppsala University Hospital, Uppsala, Sweden
(4)
Department of Urology, Länssjukhuset Ryhov, Jönköping, Jönköping, Sweden
(5)
Department of Medical Biosciences, Pathology Umeå University, Umeå, Sweden
(6)
Departemnt of Urology, Sundsvall Hospital, Sundsvall, Sweden
(7)
Department of Surgical and Perioperative Sciences, Urology and Andrology, Umeå University, Umeå, Sweden

References

  1. 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.PubMedPubMed CentralView ArticleGoogle Scholar
  2. 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.PubMedView ArticleGoogle Scholar

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