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Russell_2022_ImmInvest_Automated analysis of PD-1 and PD-L1 in lymph nodes and the microenvironment of transmissible tumours in Tasmanian devils.pdf (1.74 MB)

Automated Analysis of PD1 and PDL1 Expression in Lymph Nodes and the Microenvironment of Transmissible Tumors in Tasmanian Devils

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posted on 2023-07-28, 05:24 authored by Grace G Russell, Chiara Palmieri, Jocelyn DarbyJocelyn Darby, Gary MorrisGary Morris, Nicholas Fountain-JonesNicholas Fountain-Jones, Ruth J Pye, Andrew FliesAndrew Flies
The wild Tasmanian devil (Sarcophilus harrisii) population has suffered a devastating decline due to two clonal transmissible cancers. The first devil facial tumor 1 (DFT1) was observed in 1996, followed by a second genetically distinct transmissible tumor, the devil facial tumor 2 (DFT2), in 2014. DFT1/2 frequently metastasize, with lymph nodes being common metastatic sites. MHC-I downregulation by DFT1 cells is a primary means of evading allograft immunity aimed at polymorphic MHC-I proteins. DFT2 cells constitutively express MHC-I, and MHC-I is upregulated on DFT1/2 cells by interferon gamma, suggesting other immune evasion mechanisms may contribute to overcoming allograft and anti-tumor immunity. Human clinical trials have demonstrated PD1/PDL1 blockade effectively treats patients showing increased expression of PD1 in tumor draining lymph nodes, and PDL1 on peritumoral immune cells and tumor cells. The effects of DFT1/2 on systemic immunity remain largely uncharacterized. This study applied the open-access software QuPath to develop a semiautomated pipeline for whole slide analysis of stained tissue sections to quantify PD1/PDL1 expression in devil lymph nodes. The QuPath protocol provided strong correlations to manual counting. PD-1 expression was approximately 10-fold higher than PD-L1 expression in lymph nodes and was primarily expressed in germinal centers, whereas PD-L1 expression was more widely distributed throughout the lymph nodes. The density of PD1 positive cells was increased in lymph nodes containing DFT2 metastases, compared to DFT1. This suggests PD1/PDL1 exploitation may contribute to the poorly immunogenic nature of transmissible tumors in some devils and could be targeted in therapeutic or prophylactic treatments.Abbreviations: PD1: programmed cell death protein 1; PDL1: programmed death ligand 1; DFT1: devil facial tumor 1; DFT2: devil facial tumor 2; DFTD: devil facial tumor disease; MCC: Matthew's correlation coefficient; DAB: diaminobenzidine; ROI: region of interest.

Funding

Cancer Research to Help Tasmanian Devils : University of Veterinary Medicine

Development of a devil facial tumour disease vaccine : University of Tasmania Foundation Inc

Donation to conduct research into Tasmanian devil vaccine undertaken at the Menzies Institute of Medical Research : The Tall Foundation

Identification of devil facial tumour-associated antigens for vaccine development : University of Tasmania Foundation Inc

Identification of host-tumour interactions driving immune evasion and survival of devil facial tumor disease : University of Tasmania

Improving the DFTD vaccine by targeting key immune signalling molecules : University of Tasmania Foundation Inc

Investigation of cancer immunotherapy for the Tasmanian devil facial tumor disease : Morris Animal Foundation

Tipping the Balance from Tolerance to Immunity for the Devil Facial Tumour : Australian Research Council | DE180100484

Select Foundation Senior Research Fellowship - Immunology : The Select Foundation

Save the Tasmanian Devil Appeal - Tasmanian Devil Vaccine research : Donation via University of Tasmania Foundation

History

Sub-type

  • Article

Publication title

Immunological Investigations

Medium

Print-Electronic

Volume

ahead-of-print

Issue

ahead-of-print

Pagination

20

eISSN

1532-4311

ISSN

0882-0139

Department/School

Menzies Institute for Medical Research

Publisher

TAYLOR & FRANCIS INC

Publication status

  • Published online

Place of publication

England

Event Venue

Menzies Institute for Medical Research, College of Health and Medicine, University of Tasmania, Hobart, Tasmania, Australia.