title: In situ tumor ablation creates an antigen source for the generation of antitumor immunity.
abstract: Tumor-destructing techniques, like radiofrequency ablation (RFA), allow eradication of large tumors. Potentially, in situ tumor destruction also can provide the immune system with an antigen source for the induction of antitumor immunity. Antigen-presenting cells could take up antigens in the periphery after which they induce specific immune responses. Recent data show that especially antigen-presenting dendritic cells are crucial for the induction of potent immune responses. However, virtually nothing is known regarding the induction of immune responses after in situ tumor destruction in mice or humans. We used the well-defined murine B16-OVA melanoma cell line to develop a novel tumor model to explore: (a). the immunologic consequences of in situ tumor destruction; and (b). the efficacy of a combination approach of tumor destruction and immunostimulation. Applying this model system we demonstrate that following RFA, a weak but detectable immune response develops, directed against OVA, but also against a broader range of B16 antigens. Adoptive transfer experiments further indicate that antitumor reactivity can be transferred to naïve mice by splenocytes. To augment the response observed, we administered a blocking monoclonal antibody against cytotoxic T-lymphocyte-associated antigen 4 at the time of tumor destruction. Interestingly, this strongly enhanced antitumor immunity, resulting in long-lasting tumor protection. These results illustrate that in situ tumor destruction can provide a useful antigen source for the induction of antitumor immunity, provided that additional immunostimulatory signals are coadministered.
authors.affiliation: Department of Tumor Immunology, Nijmegen Center for Molecular Life Sciences, Nijmegen, the Netherlands.
authors.forename: Martijn H M G M
authors.initials: MH
authors.lastname: den Brok
authors.forename: Roger P M
authors.initials: RP
authors.lastname: Sutmuller
authors.forename: Robbert
authors.initials: R
authors.lastname: van der Voort
authors.forename: Erik J
authors.initials: EJ
authors.lastname: Bennink
authors.forename: Carl G
authors.initials: CG
authors.lastname: Figdor
authors.forename: Theo J M
authors.initials: TJ
authors.lastname: Ruers
authors.forename: Gosse J
authors.initials: GJ
authors.lastname: Adema
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000276:immunology; D000951:Antigens, Neoplasm / Q000096:biosynthesis* / Q000276:immunology*; D060908:CTLA-4 Antigen; D017115:Catheter Ablation / Q000379:methods*; D006224:Cricetinae; D005260:Female; D016219:Immunotherapy, Adoptive / Q000379:methods; D007371:Interferon-gamma / Q000096:biosynthesis; D008213:Lymphocyte Activation; D008297:Male; D008546:Melanoma, Experimental / Q000276:immunology* / Q000601:surgery*; D051379:Mice; D008810:Mice, Inbred C57BL; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000943:Antigens, Differentiation; D000951:Antigens, Neoplasm; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; C556707:Ctla4 protein, mouse; D007371:Interferon-gamma