The newly-arisen Devil facial tumour disease 2 (DFT2) reveals a mechanism for the emergence of a contagious cancer.

Alison Caldwell,Maximilian R Stammnitz,Rachel S Owen,Karsten Skjødt,Gregory M Woods,Young Mi Kwon,Gareth J Thomas,Jim Kaufman,Hannah Vt Siddle,Cesar Tovar,Rachel Coleby,Elizabeth P Murchison,Marios Tringides,Tim Elliott

doi:10.7554/elife.35314

Abstract

Devil Facial Tumour 2 (DFT2) is a recently discovered contagious cancer circulating in the Tasmanian devil (Sarcophilus harrisii), a species which already harbours a more widespread contagious cancer, Devil Facial Tumour 1 (DFT1). Here we show that in contrast to DFT1, DFT2 cells express major histocompatibility complex (MHC) class I molecules, demonstrating that loss of MHC is not necessary for the emergence of a contagious cancer. However, the most highly expressed MHC class I alleles in DFT2 cells are common among host devils or non-polymorphic, reducing immunogenicity in a population sharing these alleles. In parallel, MHC class I loss is emerging in vivo, thus DFT2 may be mimicking the evolutionary trajectory of DFT1. Based on these results we propose that contagious cancers may exploit partial histocompatibility between the tumour and host, but that loss of allogeneic antigens could facilitate widespread transmission of DFT2.

Highlights

Contagious cancers have emerged and circulate in two species of mammals and four species of molluscs (Metzger et al, 2015, 2016; Novinski, 1876; Pearse and Swift, 2006)
Flow cytometry using a monoclonal antibody against Tasmanian devil b2m was used to assess the level of major histocompatibility complex (MHC) class I expression on the surface of a representative Devil Facial Tumour 1 (DFT1) cell line (DFT1_4906) (Figure 1A), DFT1 cells treated with IFNg (DFT1_4906 + IFNg) (Figure 1B), three Devil Facial Tumour 2 (DFT2) cell lines (DFT2_RV, DFT2_SN and DFT2_TD549) (Figure 1C,D and E) and devil fibroblast cells (Fibroblasts_Salem) (Figure 1F)
These results indicate that DFT2 cells grown in culture express surface MHC class I molecules in contrast to DFT1, which is MHC class I negative

Summary

Introduction

Contagious cancers have emerged and circulate in two species of mammals (dogs and Tasmanian devils) and four species of molluscs (Metzger et al, 2015, 2016; Novinski, 1876; Pearse and Swift, 2006). Biochemical tests showed that the DFT2 cells do carry MHCs, but that the MHC barcodes of DFT2 are similar to those of the devils infected with the disease This finding may explain how the cancer can spread undetected in these animals, because the immune system does not recognize it as coming from outside the body. Subsequent cytokine signalling leads to lymphocyte infiltration of tumours, MHC up-regulation and either tumour regression or stasis of growth (Yang et al, 1987) These findings have suggested that loss of MHC class I expression is necessary for the emergence and subsequent transmission of contagious cancers. Why DFT2 cells can pass between individuals without a protective immune response from the host is not known, nor are the conditions that have facilitated the emergence of two contagious cancers in this species. DFT2 tumours were identified with evidence of MHC class I loss, indicating the emergence of MHC class I down-regulation in this tumour

Results

Discussion

Materials and methods