EXPLORING THE ROLES OF XENOPUS MHC CLASS I-LIKE MOLECULES AND INNATE-LIKE T CELLS IN TUMOR IMMUNITY
Maureen Banach, University of Rochester Medical Center
Maureen Banach, Eva-Stina Edholm, PhD, Jacques Robert, PhD, Department of Microbiology & Immunology, University of Rochester Medical Center, Rochester, NY
The stimulation of natural killer T, so called innate-like (i) T cells, is a new therapeutic approach against some types of human cancers. However, the results are so far ambiguous because the conditions leading to either an anti- or pro-tumoral activity of these cells are only superficially understood. As iT cells recognize and interact with MHC class I-like molecules, it is also puzzling that many cancers highly express these molecules. To gain better insights into fundamental functions of iT and class I-like molecules, we use a comparative tumor immunity model in the amphibian Xenopus. Using RNA interference (RNAi) technology, we previously demonstrated that one of Xenopus MHC class I-like (XNC) genes, XNC10, is critical for the development and function of iT cells, expressing an invariant T cell receptor (TCR) α chain rearrangement – Vα6-Jα1.43. Furthermore, our data suggests that another iT cell subset, characterized by the invariant TCR rearrangement – Vα22-Jα1.32 is specifically involved in the immunity against Xenopus thymic lymphoid tumors. The intraperitoneal transplantation of Xenopus tumor cells into syngeneic tadpoles resulted in significant early infiltration of both Vα6- Jα1.43 and Vα22-Jα1.32, concomitant with the decrease of these subsets from spleen and thymus. We hypothesize that by impairing the tumor expression of XNC10 and/or other XNC genes, the infiltration of specific iT cell subsets might be manipulated. To explore this possibility we are developing a reverse genetic approach with RNAi and three-component CRISPR/Cas9 system to generate transgenic animals deficient in Vα22 iT cells and tumor lines stably deficient in specific XNC genes.