Journal article

Macrophage-Derived CXCL9 and CXCL10 Are Required for Antitumor Immune Responses Following Immune Checkpoint Blockade

Imran G House, Peter Savas, Junyun Lai, Amanda XY Chen, Amanda J Oliver, Zhi L Teo, Kirsten L Todd, Melissa A Henderson, Lauren Giuffrida, Emma V Petley, Kevin Sek, Sherly Mardiana, Tuba N Gide, Camelia Quek, Richard A Scolyer, Georgina V Long, James S Wilmott, Sherene Loi, Phillip K Darcy, Paul A Beavis

Clinical Cancer Research | AMER ASSOC CANCER RESEARCH | Published : 2020

Abstract

PURPOSE: Response rates to immune checkpoint blockade (ICB; anti-PD-1/anti-CTLA-4) correlate with the extent of tumor immune infiltrate, but the mechanisms underlying the recruitment of T cells following therapy are poorly characterized. A greater understanding of these processes may see the development of therapeutic interventions that enhance T-cell recruitment and, consequently, improved patient outcomes. We therefore investigated the chemokines essential for immune cell recruitment and subsequent therapeutic efficacy of these immunotherapies. EXPERIMENTAL DESIGN: The chemokines upregulated by dual PD-1/CTLA-4 blockade were assessed using NanoString-based analysis with results confirmed a..

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Grants

Awarded by National Health and Medical Research Council (NHMRC)


Awarded by National Breast Cancer Foundation


Awarded by National Breast Cancer Foundation Fellowship


Awarded by NHMRC Senior Research Fellowship


Funding Acknowledgements

The authors would like to acknowledge the assistance of the Animal Facility technicians at the Peter MacCallum Cancer Centre. This work was funded by a Program Grant from the National Health and Medical Research Council (NHMRC; grant number 1132373) and a National Breast Cancer Foundation Grant (IIRS-19016 19-22). P.A. Beavis is supported by National Breast Cancer Foundation Fellowship (ID#ECF-17-005). P.K. Darcy is supported by an NHMRC Senior Research Fellowship (APP1136680).