Journal article

Tissue-specific tumor microenvironments influence responses to immunotherapies

Amanda J Oliver, Ashleigh S Davey, Simon P Keam, Sherly Mardiana, Jack D Chan, Bianca von Scheidt, Paul A Beavis, Imran G House, Jonas RM Van Audernaerde, Phillip K Darcy, Michael H Kershaw, Clare Y Slaney

Clinical & Translational Immunology | WILEY | Published : 2019

Abstract

Objectives: Investigation of variable response rates to cancer immunotherapies has exposed the immunosuppressive tumor microenvironment (TME) as a limiting factor of therapeutic efficacy. A determinant of TME composition is the tumor location, and clinical data have revealed associations between certain metastatic sites and reduced responses. Preclinical models to study tissue-specific TMEs have eliminated genetic heterogeneity, but have investigated models with limited clinical relevance. Methods: We investigated the TMEs of tumors at clinically relevant sites of metastasis (liver and lungs) and their impact on αPD-1/αCTLA4 and trimAb (αDR5, α4-1BB, αCD40) therapy responses in the 67NR mous..

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Grants

Awarded by Cancer Australia


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


Awarded by National Breast Cancer Foundation (NBCF) of Australia


Awarded by Susan G Komen Breast Cancer Foundation


Awarded by Research Foundation Flanders


Funding Acknowledgements

This work was supported by grants from Cancer Australia (1100199), the Peter MacCallum Cancer Center Foundation, the National Health and Medical Research Council (NHMRC) of Australia (program grant number 1132373), the National Breast Cancer Foundation (NBCF) of Australia (IIRS-18-064) and Susan G Komen Breast Cancer Foundation (16376637). AJO was supported by an Australian Postgraduate Award. PKD and MHK were supported by NHMRC Senior Research Fellowships. CYS and PAB were supported by a postdoctoral fellowship from the NBCF. SPK was supported by a Cancer Council Victoria Grant-in-aid. JRMVA is a Research fellow of the Research Foundation Flanders (1S32316N).