Selective suppression of melanoma lacking IFN-γ pathway by JAK inhibition depends on T cells and host TNF signaling

Hongxing Shen; Fengyuan Huang; Xiangmin Zhang; Oluwagbemiga A. Ojo; Yuebin Li; Hoa Quang Trummell; Joshua C. Anderson; John Fiveash; Markus Bredel; Eddy S. Yang; Christopher D. Willey; Zechen Chong; James A. Bonner; Lewis Zhichang Shi

doi:10.1038/s41467-022-32754-7

Nature Communications (Aug 2022)

Selective suppression of melanoma lacking IFN-γ pathway by JAK inhibition depends on T cells and host TNF signaling

Hongxing Shen,
Fengyuan Huang,
Xiangmin Zhang,
Oluwagbemiga A. Ojo,
Yuebin Li,
Hoa Quang Trummell,
Joshua C. Anderson,
John Fiveash,
Markus Bredel,
Eddy S. Yang,
Christopher D. Willey,
Zechen Chong,
James A. Bonner,
Lewis Zhichang Shi

Affiliations

Hongxing Shen: Department of Radiation Oncology, Heersink School of Medicine, University of Alabama at Birmingham (UAB-SOM)
Fengyuan Huang: Department of Genetics and Informatics Institute
Xiangmin Zhang: Department of Pharmaceutical Sciences, Wayne State University
Oluwagbemiga A. Ojo: Department of Radiation Oncology, Heersink School of Medicine, University of Alabama at Birmingham (UAB-SOM)
Yuebin Li: Department of Radiation Oncology, Heersink School of Medicine, University of Alabama at Birmingham (UAB-SOM)
Hoa Quang Trummell: Department of Radiation Oncology, Heersink School of Medicine, University of Alabama at Birmingham (UAB-SOM)
Joshua C. Anderson: Department of Radiation Oncology, Heersink School of Medicine, University of Alabama at Birmingham (UAB-SOM)
John Fiveash: Department of Radiation Oncology, Heersink School of Medicine, University of Alabama at Birmingham (UAB-SOM)
Markus Bredel: Department of Radiation Oncology, Heersink School of Medicine, University of Alabama at Birmingham (UAB-SOM)
Eddy S. Yang: Department of Radiation Oncology, Heersink School of Medicine, University of Alabama at Birmingham (UAB-SOM)
Christopher D. Willey: Department of Radiation Oncology, Heersink School of Medicine, University of Alabama at Birmingham (UAB-SOM)
Zechen Chong: Department of Genetics and Informatics Institute
James A. Bonner: Department of Radiation Oncology, Heersink School of Medicine, University of Alabama at Birmingham (UAB-SOM)
Lewis Zhichang Shi: Department of Radiation Oncology, Heersink School of Medicine, University of Alabama at Birmingham (UAB-SOM)

DOI: https://doi.org/10.1038/s41467-022-32754-7
Journal volume & issue: Vol. 13, no. 1
pp. 1 – 17

Abstract

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Tumor loss of IFN-γ signalling is a major mechanism of resistance to immune checkpoint blockers. Here the authors report that melanoma cells with knockout of IFNγR1 show constitutive JAK1/2 activation and that the JAK1/2 inhibitor ruxolitinib can overcome resistance to anti-CTLA-4 therapy.

Published in Nature Communications

ISSN: 2041-1723 (Online)
Publisher: Nature Portfolio
Country of publisher: United Kingdom
LCC subjects: Science
Website: https://www.nature.com/ncomms/

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