Tumorigenesis and anti-tumor immune responses in Xenopus

Abstract

Despite intense study, the role of the immune system in detecting (immunosurveillance), controlling and remodeling (immunoediting) neoplasia remains elusive. We present here a comparative view of the complex interactions between neoplasia and the host immune system. We provide evidence, in the amphibian Xenopus laevis, consistent with an evolutionarily conserved and crucial role of the immune system in controlling neoplasia, which involves a striking variety of anti-tumoral immune effectors including conventional CTLs, classical MHC class Ia unrestricted CTLs (CCU-CTLs) that interact with nonclassical MHC class Ib molecules, CD8 NKT-like cells and NK cells. We also review the tumors found in X. laevis with an emphasis on thymic lymphoid tumors and a rare ovarian dysgerminoma. Finally, we consider the use of X. laevis for in vivo study of tumorigenesis. Given our current knowledge, the experimental systems already established in X. laevis, and the rapid accumulation of genetic resources for the sister species Silurana (Xenopus) tropicalis, it is our conviction that these species provide an ideal alternative to the murine system for studying tumorigenesis and tumor immunity.

Semi-solid tumor model in Xenopus laevis/gilli cloned tadpoles for intravital study of neovascularization, immune cells and melanophore infiltration

“…The 15/0 thymic lymphoid tumor and the Xenopus host immune response are relatively well characterized (reviewed in (Goyos and Robert, 2009)). Here, we have established the initial conditions to visualize in real time the active formation of the tumor microenvironment induced by 15/0 tumor cells including neovascularization, collagen rearrangements as well as infiltration of melanophores.…”

“…Importantly, X. laevis is the only known amphibian species with spontaneously arising and transplantable lymphoid tumors (Goyos and Robert, 2009). The 15/0 tumor cell line was derived from a spontaneous thymic tumor in the LG-15 clone (Robert et al, 1994).…”

Exploring the functions of nonclassical MHC class Ib genes in Xenopus laevis by the CRISPR/Cas9 system

“…We designed a single guide RNA (sgRNA) against XNC10.1 α2 domain in order to efficiently knock out the XNC10.1 gene product. Furthermore, we previously found that both XNC11 (Goyos et al 2009) and XNC1 (unpublished observations) are highly expressed by immature thymocytes, which in mammals is a hallmark of class Ib-mediated iT cell development, and by Xenopus thymus-derived lymphoid tumor cell lines. This suggests important immune functions, possibly critical for the development and function of distinct iT cell subsets.…”

“…To explore this possibility, we targeted another XNC gene XNC11 at the same time as XNC10.1 . We chose XNC11 because it also highly expressed by immature thymocytes and X. laevis thymic lymphoid tumor cell lines (Edholm et al, 2014; Goyos and Robert, 2009). Whether XNC11 plays a redundant function of XNC10.1 or is required for the development of some distinct subpopulation of iT cells remains to be determined.…”

Maternal uterine natural killer cells nurture fetal growth: in medio stat virtus

“…NK cells may not have evolved to orchestrate placentation, but rather to control and fight infections. NK-like cells with natural cytotoxicity directed at allogeneic targets are found in amphibians and fish, which pre-date placenta-bearing mammals [54,55]. Phylogenetic evidence strongly suggests that the ancestral form of placentation has been invasive and involved direct contact of maternal blood with placental trophoblasts throughout gestation (hemochorial) [56].…”