Abstract

Transmissible Cancers and the Immunogenic Role of Trypanosoma cruzi Calreticulin: C1q Binding in Canine Transmissible Venereal Tumor Cells Mediated by TcCRT Cruz P.1, Torres C.2, Ferreira A.1 1 Laboratory of Immunology of Microbial Aggression, ICBM, Faculty of Medicine, University of Chile 2 Laboratory of Biomedicine and Regenerative Medicine, Faculty of Veterinary Medicine, University of Chile Introduction Transmissible cancers are important due to both their capacity to be easily spread among allogenic individuals, and their significant potential for endangering wildlife. Canine transmissible venereal tumor (CTVT) and the Australian devil facial tumor disease (DFTD) are transmissible cancers naturally occurring in domestic dogs (Canis lupus familiaris) and Tasmanian devils (Sarcophilus harrisii), respectively. Here, we investigate whether Trypanosoma cruzi calreticulin (TcCRT), known by its anti-angiogenic and anti-tumoral effects, increases the immunogenicity of CTVT cells. We examined TcCRT surface binding and the subsequent engagement of human C1q (HuC1q), a potent opsonin mediating engulfment by antigen presenting cells (APCs). In the regional lymph nodes these APCs will promote cytotoxic T cell responses resulting in significant tumor growth inhibition. Materials and Methods A primary CTVT cell line was established from clinical samples obtained at Veterinary Teaching Hospital, University of Chile. Exogenous binding of rTcCRT and HuC1q was assessed by flow cytometry using FITC-conjugated rTcCRT or FITC- and PE-conjugated secondary antibodies. Results rTcCRT binds to the CTVT cells and it is subsequently recognized by HuC1q. Conclusion and Future Directions rTcCRT binds to the CTVT cells surface and forms a complex with C1q, representing an important first stage for efficient CTVT cell phagocytosis. This could potentially lead to increased tumor phagocytosis, and the presentation of tumor- and rTcCRT-derived peptides to T cells in an appropriate MHC context. We propose that this process, aided by intratumor rTcCRT inoculation, may antagonize the characteristic immune evasiveness of CTVT leading to tumor rejection by cytotoxic mechanisms. Supported by a National Doctoral Scholarship (Cruz P.) and a Regular FONDECYT Project 1130099 (CONICYT-Chile).