gamma delta T Cells in Merkel Cell Carcinomas Have a Proinflammatory Profile Prognostic of Patient Survival

Nicholas A Gherardin; Kelly Waldeck; Alex Caneborg; Luciano G Martelotto; Shiva Balachander; Magnus Zethoven; Pasquale M Petrone; Andrew Pattison; James S Wilmott; Sergio M Quinones-Parra; Fernando Rossello; Atara Posner; Annie Wong; Alison M Weppler; Kerwin F Shannon; Angela Hong; Peter M Ferguson; Valerie Jakrot; Jeanette Raleigh; Athena Hatzimihalis; Paul J Neeson; Paolo Deleso; Meredith Johnston; Margaret Chua; Juergen C Becker; Shahneen Sandhu; Grant A McArthur; Anthony J Gill; Richard A Scolyer; Rodney J Hicks; Dale Godfrey; Richard W Tothill

Journal article

gamma delta T Cells in Merkel Cell Carcinomas Have a Proinflammatory Profile Prognostic of Patient Survival

Nicholas A Gherardin, Kelly Waldeck, Alex Caneborg, Luciano G Martelotto, Shiva Balachander, Magnus Zethoven, Pasquale M Petrone, Andrew Pattison, James S Wilmott, Sergio M Quinones-Parra, Fernando Rossello, Atara Posner, Annie Wong, Alison M Weppler, Kerwin F Shannon, Angela Hong, Peter M Ferguson, Valerie Jakrot, Jeanette Raleigh, Athena Hatzimihalis Show all

CANCER IMMUNOLOGY RESEARCH | AMER ASSOC CANCER RESEARCH | Published : 2021

DOI: 10.1158/2326-6066.CIR-20-0817

Abstract

Merkel cell carcinomas (MCC) are immunogenic skin cancers associated with viral infection or UV mutagenesis. To study T-cell infiltrates in MCC, we analyzed 58 MCC lesions from 39 patients using multiplex-IHC/immunofluorescence (m-IHC/IF). CD4+ or CD8+ T cells comprised the majority of infiltrating T lymphocytes in most tumors. However, almost half of the tumors harbored prominent CD4/CD8 double-negative (DN) T-cell infiltrates (>20% DN T cells), and in 12% of cases, DN T cells represented the majority of T cells. Flow cytometric analysis of single-cell suspensions from fresh tumors identified DN T cells as predominantly Vδ2- γδ T cells. In the context of γδ T-cell inflammation, these cells ..

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University of Melbourne Researchers

Dale Godfrey Author Microbiology and Immunology

Grant McArthur Author Melbourne Medical School

Fernando Rossello Author Clinical Pathology

Nicholas Gherardin Author Microbiology and Immunology

Richard Tothill Author Clinical Pathology

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RESEARCH FELLOWSHIP

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Grants

Awarded by National Health and Medical Research Council of Australia (NHMRC)

Awarded by Australian Research Council (ARC)

Awarded by NHMRC

Awarded by Medical Research Future Fund

Funding Acknowledgements

The authors are grateful to following people: Dr. Paul Savage (Brigham Young University, Provo, UT, USA) for providing a-galactosylceramide analogue PBS44 used for production of CD1d-a-GalCer tetramers; Prof. David Fairlie (University of Queensland, Brisbane, Queensland, Australia) for providing 5-ARU used for production of MR1-5-OP-RU tetramers; staff from the flow cytometry facilities at the Department of Microbiology and Immunology at the Peter Doherty Institute and the Melbourne Brain Centre, both at the University of Melbourne, as well as the Peter MacCallum Cancer Centre; University ofMelbourne Centre for Cancer Research and Peter MacCallum Cancer Centre Genomics Core Facilities and the Genomics Platform Group at University of Melbourne for their support in generating primary data; Stephen Fox at the Peter MacCallum Cancer Centre for patient samples; Paul Nghiem, Kelly Paulson, and Kristina Lachance at the Fred Hutchinson Cancer Research Center for providing clinical annotation for their published MCC microarray data. This work was supported by the National Health and Medical Research Council of Australia (NHMRC; 1113293) and the Australian Research Council (ARC; CE140100011). D.I. Godfrey was supported by an NHMRC Senior Principal Research Fellowship (1020770, 1117766). R.A. Scolyer is supported by an NHMRC Program Grant, Practitioner Fellowship (1141295), the Ainsworth Foundation, the ClearBRIDGE Foundation, the Cameron Family, and colleagues at Melanoma Institute Australia and Royal Prince Alfred Hospital. R.J. Hicks is supported by an NHMRC Practitioner Fellowship (1108050). R.W. Tothill is supported by a Victorian Cancer Agency Mid-Career Fellowship and has received funding from the Melanoma and Skin Service group at Peter MacCallum Cancer Centre, the University of Melbourne (Research Support Grant Scheme), and theMedical Research Future Fund (1169955). A. Pattison is supported by the Joseph Herman Trust at the University of Melbourne.