title: Chemotherapy enhances cross-presentation of nuclear tumor antigens.
abstract: Cross-presentation of tumor antigen is essential for efficient priming of naïve CD8⁺ T lymphocytes and induction of effective anti-tumor immunity. We hypothesized that the subcellular location of a tumor antigen could affect the efficiency of cross-presentation, and hence the outcome of anti-tumor responses to that antigen. We compared cross-presentation of a nominal antigen expressed in the nuclear, secretory, or cytoplasmic compartments of B16 melanoma tumors. All tumors expressed similar levels of the antigen. The antigen was cross-presented from all compartments but when the concentration was low, nuclear antigen was less efficiently cross-presented than antigen from other cellular locations. The efficiency of cross-presentation of the nuclear antigen was improved following chemotherapy-induced tumor cell apoptosis and this correlated with an increase in the proportion of effector CTL. These data demonstrate that chemotherapy improves nuclear tumor antigen cross-presentation and could be important for anti-cancer immunotherapies that target nuclear antigens.
authors.affiliation: National Centre for Asbestos Related Diseases (NCARD), QEII Medical Centre, Nedlands, Western Australia; School of Medicine and Pharmacology, University of Western Australia, QEII Medical Centre, Nedlands, Western Australia.
authors.forename: Chidozie C
authors.initials: CC
authors.lastname: Anyaegbu
authors.affiliation: National Centre for Asbestos Related Diseases (NCARD), QEII Medical Centre, Nedlands, Western Australia; School of Medicine and Pharmacology, University of Western Australia, QEII Medical Centre, Nedlands, Western Australia.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Lake
authors.affiliation: School of Pathology and Laboratory Medicine, University of Western Australia, QEII Medical Centre, Nedlands, Western Australia.
authors.forename: Kathy
authors.initials: K
authors.lastname: Heel
authors.affiliation: National Centre for Asbestos Related Diseases (NCARD), QEII Medical Centre, Nedlands, Western Australia; School of Medicine and Pharmacology, University of Western Australia, QEII Medical Centre, Nedlands, Western Australia.
authors.forename: Bruce W
authors.initials: BW
authors.lastname: Robinson
authors.affiliation: National Centre for Asbestos Related Diseases (NCARD), QEII Medical Centre, Nedlands, Western Australia; School of Medicine and Pharmacology, University of Western Australia, QEII Medical Centre, Nedlands, Western Australia.
authors.forename: Scott A
authors.initials: SA
authors.lastname: Fisher
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000096:biosynthesis / Q000276:immunology*; D034961:Antigens, Nuclear / Q000096:biosynthesis / Q000276:immunology*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D045142:Cross-Priming / Q000276:immunology; D005260:Female; D008546:Melanoma, Experimental / Q000188:drug therapy* / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic
chemical_list: D000951:Antigens, Neoplasm; D034961:Antigens, Nuclear; D000970:Antineoplastic Agents