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Sökning: id:"swepub:oai:DiVA.org:umu-139039" > B cells in tumor dr...

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

Zirakzadeh, A. Ali (författare)
Krantz, David (författare)
Winerdal, Malin (författare)
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Lundgren, Christian (författare)
Hartana, Ciputra (författare)
Ahlén Bergman, Emma (författare)
Hansson, Johan (författare)
Holmström, Benny (författare)
Sidiki, Alexander (författare)
Vasko, Janos (författare)
Umeå universitet,Patologi
Johansson, Markus (författare)
Marits, Per (författare)
Sherif, Amir (författare)
Umeå universitet,Urologi och andrologi
Winqvist, Ola (författare)
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 (creator_code:org_t)
BioMed Central, 2015
2015
Engelska.
Ingår i: Journal for ImmunoTherapy of Cancer. - : BioMed Central. - 2051-1426. ; 3:Suppl 2
  • Tidskriftsartikel (refereegranskat)
Abstract Ämnesord
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  • 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.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Urologi och njurmedicin (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Urology and Nephrology (hsv//eng)

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