Chemotherapy enhances cross-presentation of nuclear tumor antigens

• Published in: PloS one Vol. 9; no. 9; p. e107894
• Main Authors: Anyaegbu, Chidozie C, Lake, Richard A, Heel, Kathy, Robinson, Bruce W, Fisher, Scott A
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 22.09.2014; Public Library of Science (PLoS)
• Subjects: Animals; Anticancer properties; Antigen (tumor-associated); Antigen presentation; Antigens; Antigens, Neoplasm - biosynthesis; Antigens, Neoplasm - immunology; Antigens, Nuclear - biosynthesis; Antigens, Nuclear - immunology; Antineoplastic Agents - therapeutic use; Apoptosis; Asbestos; Biology and Life Sciences; Cancer; Cancer immunotherapy; CD8 antigen; CD8-Positive T-Lymphocytes - immunology; Chemotherapy; Compartments; Cross-Priming - immunology; Cytotoxicity; Efficiency; Female; Immunity; Immunotherapy; Influenza; Laboratories; Localization; Lymphatic system; Lymphocytes; Lymphocytes T; Medicine; Medicine and Health Sciences; Melanoma; Melanoma, Experimental - drug therapy; Melanoma, Experimental - immunology; Mice; Mice, Transgenic; Peptides; Pharmacology; Priming; Proteins; Rodents; T cell receptors; T cells; Tumor antigens; Tumors; Australia; Western Australia Australia; Perth Western Australia Australia
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0107894

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.