Agonism of CD11b reprograms innate immunity to sensitize pancreatic cancer to immunotherapies

Roheena Z. Panni; John M. Herndon; Chong Zuo; Samarth Hegde; Graham D. Hogg; Brett L. Knolhoff; Marcus A. Breden; Xiaobo Li; Varintra E. Krisnawan; Samia Q. Khan; Julie K. Schwarz; Buck E. Rogers; Ryan C. Fields; William G. Hawkins; Vineet Gupta; David G. DeNardo

doi:10.1126/scitranslmed.aau9240

Research ArticleCancer

Agonism of CD11b reprograms innate immunity to sensitize pancreatic cancer to immunotherapies

Roheena Z. Panni¹,
John M. Herndon²,
Chong Zuo²,
Samarth Hegde²,
Graham D. Hogg²,
Brett L. Knolhoff²,
Marcus A. Breden²,
Xiaobo Li³,
Varintra E. Krisnawan²,
Samia Q. Khan³,
Julie K. Schwarz⁴,⁵,
Buck E. Rogers⁴,⁵,
Ryan C. Fields¹,⁴,
William G. Hawkins ¹,⁴,
Vineet Gupta³,* and
David G. DeNardo ²,⁴,⁶,*,†

¹Department of Surgery, Washington University School of Medicine, St. Louis, MO 63110, USA.
²Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
³Drug Discovery Center, Department of Internal Medicine, Rush University Medical Center, Chicago, IL 60612, USA.
⁴Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO 63110, USA.
⁵Radiation Oncology, Washington University School of Medicine, St. Louis, MO 63110, USA.
⁶Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.

↵†Corresponding author: ddenardo{at}wustl.edu

↵* These authors contributed equally to this work as senior authors.

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Science Translational Medicine 03 Jul 2019:
Vol. 11, Issue 499, eaau9240
DOI: 10.1126/scitranslmed.aau9240

Roheena Z. Panni

Department of Surgery, Washington University School of Medicine, St. Louis, MO 63110, USA.

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John M. Herndon

Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.

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Chong Zuo

Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.

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Samarth Hegde

Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.

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Graham D. Hogg

Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.

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Brett L. Knolhoff

Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.

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Marcus A. Breden

Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.

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Xiaobo Li

Drug Discovery Center, Department of Internal Medicine, Rush University Medical Center, Chicago, IL 60612, USA.

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Varintra E. Krisnawan

Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.

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Samia Q. Khan

Drug Discovery Center, Department of Internal Medicine, Rush University Medical Center, Chicago, IL 60612, USA.

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Julie K. Schwarz

Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO 63110, USA.

Radiation Oncology, Washington University School of Medicine, St. Louis, MO 63110, USA.

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Buck E. Rogers

Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO 63110, USA.

Radiation Oncology, Washington University School of Medicine, St. Louis, MO 63110, USA.

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Ryan C. Fields

Department of Surgery, Washington University School of Medicine, St. Louis, MO 63110, USA.

Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO 63110, USA.

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William G. Hawkins

Department of Surgery, Washington University School of Medicine, St. Louis, MO 63110, USA.

Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO 63110, USA.

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Vineet Gupta

Drug Discovery Center, Department of Internal Medicine, Rush University Medical Center, Chicago, IL 60612, USA.

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David G. DeNardo

Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.

Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO 63110, USA.

Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.

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For correspondence: ddenardo@wustl.edu

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Agonism of CD11b reprograms innate immunity to sensitize pancreatic cancer to immunotherapies

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