Journal article

Harnessing Natural Killer Immunity in Metastatic SCLC

Sarah A Best, Jonas B Hess, Fernando Souza-Fonseca-Guimaraes, Joseph Cursons, Ariena Kersbergen, Xueyi Dong, Jai Rautela, Stephanie R Hyslop, Matthew E Ritchie, Melissa J Davis, Tracy L Leong, Louis Irving, Daniel Steinfort, Nicholas D Huntington, Kate D Sutherland



INTRODUCTION: SCLC is the most aggressive subtype of lung cancer, and though most patients initially respond to platinum-based chemotherapy, resistance develops rapidly. Immunotherapy holds promise in the treatment of lung cancer; however, patients with SCLC exhibit poor overall responses highlighting the necessity for alternative approaches. Natural killer (NK) cells are an alternative to T cell-based immunotherapies that do not require sensitization to antigens presented on the surface of tumor cells. METHODS: We investigated the immunophenotype of human SCLC tumors by both flow cytometry on fresh samples and bioinformatic analysis. Cell lines generated from murine SCLC were transplanted i..

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Awarded by Australian National Health and Medical Research Council (NHMRC)

Awarded by Cancer Australia

Awarded by NHMRC CDF2

Awarded by NHMRC Early Career Fellowship

Awarded by Victorian Cancer Agency Early Career Seed grant

Funding Acknowledgements

This work was supported by an Australian National Health and Medical Research Council (NHMRC) project grant to Drs. Sutherland, Huntington, and Steinfort (1159955); to Dr. Souza-Fonseca-Guimaraes (1140406); a Priority-Driven Collaborative Cancer Research Scheme funded by Cure Cancer Australia with the assistance of Cancer Australia (1158085); and a generous charitable donation. Dr. Sutherland is supported by the Peter and Julie Alston Centenary Fellowship, Dr. Huntington is a NHMRC CDF2 Fellow (1124788), Dr. Steinfort holds an NHMRC Early Career Fellowship (1121880), Dr. Rautela holds a Victorian Cancer Agency Early Career Seed grant (ECSG18020), and Mr. Hess is supported by a University of Melbourne Research Scholarship. This work was made possible through the Victorian State Government Operational Infrastructure Support and Australian Government NHMRC IRIISS. The authors thank Kimmy Zhao and Leanne Taylor at the Victorian Cancer Biobank for collection, deidentification, and delivery of the patient material. The authors are grateful to L. Mackiewicz, K. Hughes, L. Scott, E. Loza, L. Spencer, and D. Boyd for animal husbandry; T. Camilleri and T. Kratina for genotyping; and S. Monard in the Walter and Eliza Hall Institute (WEHI) Flow Cytometry Facility and E. Tsui in the WEHI Histology Facility for support. The authors thank T. Oliver (Huntsman Cancer Institute) for reagents and protocols. The authors also thank S. Griffiths (Royal Melbourne Hospital), M. Pelligrini (WEHI), E. Vivier (Centre d'immunologie de Marseille-Luminy), and S. Karlsson (Lund University) for generously sharing mouse strains.