Tumor Immunology Viewed from Alternative Animal Models—the Xenopus Story

Abstract

a) Purpose of review Nonmammalian comparative animal models are important not only to gain fundamental evolutionary understanding of the complex interactions of tumors with the immune system, but also to better predict the applicability of novel immunotherapeutic approaches to humans. After reviewing recent advances in developing alternative models, we focus on the amphibian Xenopus laevis and its usefulness in deciphering the perplexing roles of MHC class I-like molecules and innate (i)T cells in tumor immunity. b) Recent findings Experiments using MHC-defined inbred and cloned animals, tumor cell lines, effective reagents, sequenced genomes, and adapted gene editing techniques in Xenopus, have revealed that the critical involvement of class I-like molecules and iT cells in tumor immunity has been conserved during evolution. c) Summary Comparative studies with the X. laevis tumor immunity model can contribute to the development of better and more efficient cancer immunotherapies.

Xenopus Interferon Complex: Inscribing the Amphibiotic Adaption and Species-Specific Pathogenic Pressure in Vertebrate Evolution?

“…Recent investigations have indicated that pathogenic factors (such as by chytrid fungus and Ranavirus) are causing amphibian population decline and threaten global biodiversity [25][26][27][28][29][30][31]. This further emphasizes the need to study the amphibian immunome and its interaction with epidemic pathogens [1][2][3][32][33][34][35][36][37][38][39][40]. Amphibians have several unusual characteristics that are stimulating for immunobiological studies [32,33,35,39].…”

“…This further emphasizes the need to study the amphibian immunome and its interaction with epidemic pathogens [1][2][3][32][33][34][35][36][37][38][39][40]. Amphibians have several unusual characteristics that are stimulating for immunobiological studies [32,33,35,39]. For example, amphibians have moist and permeable skin, which also serves as an organ for respiration [33,34].…”

“…Being unique to animals from any other classes of vertebrates, amphibians not only conserve and multiply the fish-like intron-containing IFN genes, but also rapidly evolve amniote-like intronless IFN genes in three tested species [13,16,51]. Amphibians are thus critical intermediate species in IFN (and potentially other immune gene families too) evolution, in addition to their key position in studies of vertebrate development [24,35,40]. We postulate that the amphibian IFN system provides an irreplaceable model to study vertebrate immune evolution in molecular and functional diversity to cope with unprecedented immuno-physiological requirement during terrestrial adaption [11][12][13][14][15][16].…”

“…Such new function revealed by the emerging studies of antifungal and developmental regulation of amphibian IFNs will certainly promote our understanding of immune evolution in vertebrates to address current pathogenic threats causing amphibian decline [25][26][27][28][29]. Xenopus is proposed as an alternative model for cancer studies due to its evolutionary tumor immunity [35]. Antitumor activity constitutes another key function of the antiviral IFNs [6].…”

An in vivo brain–bacteria interface: the developing brain as a key regulator of innate immunity

“…We developed a Xenopus model in which we could study braindependent events in embryogenesis: the brain is removed during early embryonic stages, but the animal can be kept alive and development continues. The ability of this vertebrate, a popular model for numerous biomedical contexts, [27][28][29][30][31][32][33][34] to survive and develop without a brain provides a unique opportunity to understand the role of the brain in diverse systems-level outcomes. Our prior research into brain-dependent developmental signaling revealed that the nascent brain, even before being fully formed, plays an instructive role in patterning somitic muscle and peripheral neural networks.…”