Most tumor-associated antigens (TAA) are self-molecules that are abnormally expressed in cancer cells and thus become targets of anti-tumor immune responses. Antibodies and T cells specific for some TAA have also been found in healthy individuals and associated with lowered lifetime risk for developing cancer. Lower risk for cancer has also been associated with a history of febrile viral diseases. We hypothesized that virus infections could lead to transient expression of abnormal forms of self molecules, some of which are TAAs, and facilitated by the adjuvant effects of infection and inflammation, elicit specific antibodies and T cells and lasting immune memory against those antigens simultaneously with immunity against viral antigens. Such infection-induced immune memory for TAA would be expected to provide life-long immune surveillance of cancer. Using influenza virus infection in mice as a model system, we tested this hypothesis and demonstrated that influenza experienced mice control 3LL mouse lung tumor challenge better then infection naive control mice. Using 2D-Difference Gel Electrophoresis (2D-DIGE) and mass spectrometry, we identified numerous molecules on the 3LL tumor cells recognized by antibodies elicited by two successive influenza infections, some of which were already known tumor antigens. We studied in more detail immune responses against GAPDH, Histone H4, HSP90, Malate Dehydrogenase 2 and Annexin A2, which were all overexpressed in influenza infected lungs compared to normal lungs, as well as in tumor cells. Lastly, we show that immune responses generated through vaccination against peptides derived from these antigens correlated with improved tumor control.
- Received August 13, 2013.
- Revision received November 18, 2013.
- Accepted November 18, 2013.
- Copyright © 2013, American Association for Cancer Research.