Abstract 4163: Chemokine and cytokine levels among lung cancer cases responsive to HPV antigen stimulation

Abstract

Abstract Purpose: Human papillomavirus (HPV), the causative agent for anogenital and certain head and neck cancers, has been detected in lung tumors, but its role as an etiologic agent for lung cancer remains controversial. The lung is often subjected to exogenous inflammatory insults, and patients with chronic lung inflammation have an increased risk for cancer. In addition to the genomic instability that can be caused by HPV oncoproteins, the immunomodulatory impacts of HPV infection may foster a pro-inflammatory state that increases lung cancer risk. We sought to identify such immunomodulatory effects by examining the differences in lymphocyte and cytokine/chemokine profiles between lung cancer cases and HPV-vaccinated healthy controls. Methods: Peripheral blood mononuclear cells were isolated from 22 newly diagnosed lung cancer cases and 11 healthy controls who had prior exposure to HPV antigens (immunized with Gardasil). Cells were enumerated via a hemacytometer, and were exposed to media alone or to 3 doses of Gardasil for 20 hours as an HPV challenge. Interleukin (IL-) 4, IFN-γ, and IL-17A secreting cells were then quantified using enzyme linked immunocell spot (ELISpot) analysis. Individuals were categorized as HPV-responsive if the HPV challenge resulted in an increase in at least 2 types of secreting cells, compared to media-exposed cells. The Milliplex human cytokine detection kit was used to assess circulating levels of 38 key cytokines in the plasma of cases and controls. Cytokine levels among HPV-responsive and HPV-non-responsive cases were compared. Survival analysis was also conducted. Results: All 11 HPV-vaccinated controls demonstrated an increase in cells secreting IFN-γ and IL-4. Of the 22 cases, 13 (59%) were classified as HPV-responsive, with 2 cases displaying an increase in IFN-γ and IL-4 secreting cells upon HPV challenge. Levels of TGF-α, IL-10, IL-3, IL-5, and IL-7 were significantly higher among HPV-responsive compared to non-responsive cases. Significant survival differences were also observed by HPV-responsiveness and cytokine levels. Conclusions: HPV clearly has substantial effects on the host's systemic immune response. Our study may explain whether and how the pathogenic process differs between HPV-infected and -uninfected lung tumors. Citation Format: Michael E. Scheurer, E Susan Amirian, Paul Porter, David B. Corry. Chemokine and cytokine levels among lung cancer cases responsive to HPV antigen stimulation. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4163. doi:10.1158/1538-7445.AM2014-4163