title: Doxorubicin enhances the capacity of B cells to activate T cells in urothelial urinary bladder cancer.
abstract: Cancer is currently treated by a combination of therapies, including chemotherapy which is believed to suppress the immune system. Combination of immunotherapy and chemotherapy correlates with improved survival but needs careful planning in order to achieve a synergistic effect. In this study, we have demonstrated that doxorubicin treatment of B cells resulted in increased expression of CD86 and concordantly increased CD4+T cell activation in the presence of superantigen, an effect that was inhibited by the addition of a CD86 blocking antibody. Furthermore, doxorubicin resulted in decreased expression of the anti-inflammatory cytokines IL-10 and TNF-α. Finally, B cells from urinary bladder cancer patients, treated with a neoadjuvant regiment containing doxorubicin, displayed increased CD86-expression. We conclude that doxorubicin induces CD86 expression on B cells and hence enhances their antigen-presenting ability in vitro, a finding verified in patients. Development of tailored time and dose schedules may increase the effectiveness of combining chemotherapy and immunotherapy.
authors.affiliation: Department of Medicine, Unit of Immunology and Allergy, Karolinska Institutet, Stockholm, Sweden.
authors.forename: A Ali
authors.initials: AA
authors.lastname: Zirakzadeh
authors.affiliation: Department of Medicine, Unit of Immunology and Allergy, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Johan
authors.initials: J
authors.lastname: Kinn
authors.affiliation: Department of Medicine, Unit of Immunology and Allergy, Karolinska Institutet, Stockholm, Sweden.
authors.forename: David
authors.initials: D
authors.lastname: Krantz
authors.affiliation: Department of Surgical and Perioperative Sciences, Urology and Andrology, Umeå University Hospital, Umeå, Sweden; Department of Urology, Stockholm South General Hospital, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Robert
authors.initials: R
authors.lastname: Rosenblatt
authors.affiliation: Department of Medicine, Unit of Immunology and Allergy, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Malin E
authors.initials: ME
authors.lastname: Winerdal
authors.affiliation: Department of Medicine, Unit of Immunology and Allergy, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Jin
authors.initials: J
authors.lastname: Hu
authors.affiliation: Department of Medicine, Unit of Immunology and Allergy, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Ciputra Adijaya
authors.initials: CA
authors.lastname: Hartana
authors.affiliation: Department of Medicine, Unit of Immunology and Allergy, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Christian
authors.initials: C
authors.lastname: Lundgren
authors.affiliation: Department of Medicine, Unit of Immunology and Allergy, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Emma Ahlén
authors.initials: EA
authors.lastname: Bergman
authors.affiliation: Department of Urology, Sundsvall Hospital, Sundsvall, Sweden.
authors.forename: Markus
authors.initials: M
authors.lastname: Johansson
authors.affiliation: Department of Urology, Akademiska University Hospital, Uppsala, Sweden.
authors.forename: Benny
authors.initials: B
authors.lastname: Holmström
authors.affiliation: Centre for Research and Development, Faculty of Medicine, Uppsala University, County Council of Gävleborg, Uppsala, Sweden.
authors.forename: Johan
authors.initials: J
authors.lastname: Hansson
authors.affiliation: Department of Urology, Länssjukhuset Ryhov, Region Jönköping, Sweden.
authors.forename: Alexander
authors.initials: A
authors.lastname: Sidikii
authors.affiliation: Department of Medical Biosciences, Pathology, Umeå University, Umeå, Sweden.
authors.forename: Janos
authors.initials: J
authors.lastname: Vasko
authors.affiliation: Department of Medicine, Unit of Immunology and Allergy, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Per
authors.initials: P
authors.lastname: Marits
authors.affiliation: Department of Surgical and Perioperative Sciences, Urology and Andrology, Umeå University Hospital, Umeå, Sweden.
authors.forename: Amir
authors.initials: A
authors.lastname: Sherif
authors.affiliation: Department of Medicine, Unit of Immunology and Allergy, Karolinska Institutet, Stockholm, Sweden. Electronic address: ola.winqvist@karolinska.se.
authors.forename: Ola
authors.initials: O
authors.lastname: Winqvist
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D017951:Antigen Presentation / Q000187:drug effects / Q000276:immunology; D000938:Antigen-Presenting Cells / Q000187:drug effects / Q000276:immunology; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000276:immunology* / Q000627:therapeutic use*; D001402:B-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D051940:B7-2 Antigen / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D016753:Interleukin-10 / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000628:therapy*
chemical_list: D051940:B7-2 Antigen; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D004317:Doxorubicin
keywords: B cells; CD86; Doxorubicin; Immunology; Neoadjuvant chemotherapy; Urinary bladder cancer