Impacts of the MHC class I-like XNC10 and innate-like T cells on tumor tolerance and rejection in the amphibian Xenopus

• Published in: Carcinogenesis (New York) Vol. 40; no. 7; pp. 924 - 935
• Main Authors: Banach, Maureen, Edholm, Eva-Stina, Gonzalez, Xavier, Benraiss, Abdellatif, Robert, Jacques
• Format: Journal Article
• Language: English
• Published: England Oxford University Press 20.07.2019
• Subjects: Animals; Animals, Genetically Modified; Basale medisinske, odontologiske og veterinærmedisinske fag: 710; Basic medical, dental and veterinary science disciplines: 710; Cell Line, Tumor - transplantation; Disease Models, Animal; Gene Knockout Techniques; Histocompatibility Antigens Class I - genetics; Histocompatibility Antigens Class I - immunology; Histocompatibility Antigens Class I - metabolism; Humans; Inflammation, Microenvironment and Prevention; Larva; Medical disciplines: 700; Medisinske Fag: 700; Natural Killer T-Cells - immunology; Natural Killer T-Cells - metabolism; Receptors, Antigen, T-Cell, alpha-beta - immunology; Receptors, Antigen, T-Cell, alpha-beta - metabolism; T-Lymphocyte Subsets - immunology; T-Lymphocyte Subsets - metabolism; Thymus Neoplasms - immunology; Thymus Neoplasms - pathology; Tumor Escape - immunology; VDP; Xenopus laevis; Xenopus Proteins - immunology; Xenopus Proteins - metabolism
• ISSN: 0143-3334; 1460-2180
• DOI: 10.1093/carcin/bgz100

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.