Abstract

Transmissible cancers and the immunogenic role of Trypanosoma cruzi calreticulin Cruz P., Torres C., Ferreira A. Transmissible cancers are important due to both their capacity to be easily transmitted among allogenic individuals, and their significant potential of endangering wildlife. Canine transmissible venereal tumor (CTVT) and the devil facial tumor disease (DFTD) are transmissible cancers naturally occurring in dogs (Canis lupus familiaris) and Tasmanian devils (Sarcophilus harrisii), respectively. CTVT cells evade the host immune system by secreting TGF-β1 and downregulating the expression of MHC class I molecules in tumor cells. Furthermore, tumor-secreted TGF-β1 downregulates cell-mediated cytotoxicity by impairing IFN-g secretion by T and natural killer cells. Treatments of CTVT and DFTD are complex (e.g. vincristine treatment is effective only in CTVT and recurrences are frequent). Therefore, in order to promote tumor rejection, new therapeutic or prophylactic alternatives are needed, especially in Tasmanian devils, which are under severe conservation threat due to DFTD. We have determined that Trypanosoma cruzi (the agent of American trypanosomiasis) calreticulin (TcCRT), an endoplasmic reticulum (ER) resident chaperone, is a potent anti-angiogenic and anti-tumor agent. (Indeed, TcCRT can be translocated from the ER to the parasite exterior). We have also cloned and expressed recombinant TcCRT (rTcCRT). Currently we investigate whether TcCRT promotes tumor rejection by increasing the immunogenicity of CTVT cells. We now assess the rTcCRT binding to the surface of cultured CTVT cells, with subsequent and consequent binding of complement component C1q, which opsonizes cancer cells for engulfment by dendritic cells (DCs). In the regional lymph nodes these DCs will promote cytotoxic T cell responses will resulting significant tumor growth inhibition. Supported by a National Doctoral Fellowship (P.C.) and Regular FONDECYT Project 1130099, both from CONICYT-Chile.