Chemotherapy enhances cross-presentation of nuclear tumor antigens

PLoS One. 2014 Sep 22;9(9):e107894. doi: 10.1371/journal.pone.0107894. eCollection 2014.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, Neoplasm / biosynthesis
  • Antigens, Neoplasm / immunology*
  • Antigens, Nuclear / biosynthesis
  • Antigens, Nuclear / immunology*
  • Antineoplastic Agents / therapeutic use*
  • CD8-Positive T-Lymphocytes / immunology
  • Cross-Priming / immunology
  • Female
  • Melanoma, Experimental / drug therapy*
  • Melanoma, Experimental / immunology
  • Mice
  • Mice, Transgenic

Substances

  • Antigens, Neoplasm
  • Antigens, Nuclear
  • Antineoplastic Agents

Grants and funding

This work was funded by grants from the National Health and Medical Research Council of Australia and the Insurance Commission of Western Australia. The funding bodies had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.