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.

Figure 1

Hematoxylin and eosin (H&E) staining of paraffin sections of spontaneously arising ovarian tumor in LG-15 cloned Xenopus. (A) Tumors contain nodules of round and ovoid cells with large pleomorphic nuclei as well as vacuolated roundish cells. (B) Section showing leukocyte infiltration into the ovarian stroma and the disorganized tissue architecture. (C) Higher magnification of a developing follicle with a dense layer of follicular epithelium.

Figure 2

Nucleotide and Amino Acid Alignments of 15/0 Tumor and X. laevis class Ia mRNA sequences. (A) Amino acid alignment of 15/0 and X. laevis × X. gilli LG-15 class Ia α1 domain sequences. Note: Although the LG-b/d-1 sequence is incomplete in the α1 domain it was included in the analysis. (B) Amino acid alignment of 15/0 and LG-15 class Ia α2 domain sequences. (C) Nucleotide alignment of the putative SS coding region (upstream of the α1 domain coding sequence) of the four class Ia mRNA sequences amplified from 15/0 tumor by 5’ RACE-PCR. (D) Nucleotide alignment of the putative SS and α1 domain coding regions from 15/0 tumor sequence 5-1-2 and the LG-ac/-2 allele. (E) Nucleotide alignment of the putative SS coding region from 15/0 tumor sequences 5-1-2 and 5-1-4 with a stretch in the reverse orientation of Xenopus laevis cDNA amplified from an embryonic dorsal blastopore lip library (Accession #: CO386240).