34 Tumoricidal immune response to papillomavirus-associated head and neck cancer in rabbits after intraperitoneal oxidative stress

Abstract

Background The observed regression of the papillomavirus-associated rabbit auricular VX2 carcinoma, an established model system for studying human head and neck cancer (HNSCC, head and neck squamous cell carcinoma), after intraperitoneal oxidative stress (O3/O2-Pneumoperitoneum, O3/O2-PP), led to tumor regression at a high success rate suggesting a central role of the immune system in tumor clearance. The aim of the study was to define the underlying mechanisms and steps involved in O3/O2-PP-mediated tumor regression. Material and methods After induction of VX2 tumors into the auricle of immune-competent New Zealand White Rabbits, animals were O3/O2-PP- or sham-treated. Immunohistochemical analysis of the primary VX2 tumor was performed to assess the presence of CD3+ tumor-infiltrating lymphocytes (TILs), and quantitative real-time PCR was used to monitor for 84 response genes of the innate and adaptive immune system. Finally, adoptive transfer of peripheral blood leukocytes (PBLs) derived from animals with tumor regression into control animals with progressing tumors was implemented to functionally assess the presence of acquired tumor resistance. Results O3/O2-PP treatment resulted in significant tumor regression being associated with increased levels of CD3+ TILs as well as expression of genes encoding receptors involved in pattern recognition, molecules that are required for antigen presentation and T cell activation, and inflammatory mediators. Acquired tumor resistance could be achieved in animals with newly implanted VX2 carcinoma after adoptive cell transfer of PBLs from donor rabbits with regressing tumors. Conclusion Application of intraperitoneal oxidative stress leads to an adoptively transferable, tumoricidal immune-response against the VX2 tumor tissue. Since the VX2 carcinoma is papillomavirus-associated, studying this model system could be useful in elucidating mechanisms underlying the immune-escape of HPV-driven human HNSCCs. Data of this study were recently published in the Journal Clinical Cancer Research (Rossmann et al., Clin Cancer Res, 2014).