Impacts of the MHC class I-like XNC10 and innate-like T cells on tumor tolerance and rejection in the amphibian Xenopus
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AuthorBanach, Maureen; Edholm, Eva-Stina Isabella; Gonzalez, Xavier; Benraiss, Abdellatif; Robert, Jaques
The conditions that lead to antitumor or protumor functions of natural killer T (NKT) cells against mammalian tumors are only partially understood. Therefore, insights into the evolutionary conservation of NKT and their analogs—innate-like T (iT) cells—may reveal factors that contribute to tumor eradication. As such, we investigated the amphibian Xenopus laevis iT cells and interacting MHC class I-like (XNC or mhc1b.L) genes against ff-2 thymic lymphoid tumors. Upon ff-2 intraperitoneal transplantation into syngeneic tadpoles, two iT cell subsets iVα6 and iVα22, characterized by an invariant T-cell receptor α chain rearrangement (Vα6-Jα1.43 and Vα22-Jα1.32 respectively), were recruited to the peritoneum, concomitant with a decreased level of these transcripts in the spleen and thymus. To address the hypothesize that different iT cell subsets have distinct, possibly opposing, roles upon ff-2 tumor challenge, we determined whether ff-2 tumor growth could be manipulated by impairing Vα6 iT cells or by deleting their restricting element, the XNC gene, XNC10 (mhc1b10.1.L), on ff-2 tumors. Accordingly, the in vivo depletion of Vα6 iT cells using XNC10-tetramers enhanced tumor growth, indicating Vα6 iT cell-mediated antitumor activities. However, XNC10-deficient transgenic tadpoles that also lack Vα6 iT cells were resistant to ff-2 tumors, uncovering a potential new function of XNC10 besides Vα6 iT cell development. Furthermore, the CRISPR/Cas9-mediated knockout of XNC10 in ff-2 tumors broke the immune tolerance. Together, our findings demonstrate the relevance of XNC10/iT cell axis in controlling Xenopus tumor tolerance or rejection.
This is a pre-copyedited, author-produced version of an article accepted for publication in Carcinogenesis following peer review. The version of record Banach, M., Edholm, E.-S., Gonzalez, X., Benraiss, A. & Robert, J. (2019). Impacts of the MHC class I-like XNC10 and innate-like T cells on tumor tolerance and rejection in the amphibian Xenopus. Carcinogenesis, 40(7), 924–935. is available online at: https://doi.org/10.1093/carcin/bgz100
PublisherOxford University Press
CitationBanach, Edholm ES, Gonzalez, Benraiss, Robert. Impacts of the MHC class I-like XNC10 and innate-like T cells on tumor tolerance and rejection in the amphibian Xenopus.. Carcinogenesis. 2019;40(7):924-935
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© The Author(s) 2019. Published by Oxford University Press. All rights reserved.