mTORC1 upregulates B7-H3/CD276 to inhibit antitumor T cells and drive tumor immune evasion

Heng-Jia Liu; Heng Du; Damir Khabibullin; Mahsa Zarei; Kevin Wei; Gordon J. Freeman; David J. Kwiatkowski; Elizabeth P. Henske

doi:10.1038/s41467-023-36881-7

Nature Communications (Mar 2023)

mTORC1 upregulates B7-H3/CD276 to inhibit antitumor T cells and drive tumor immune evasion

Heng-Jia Liu,
Heng Du,
Damir Khabibullin,
Mahsa Zarei,
Kevin Wei,
Gordon J. Freeman,
David J. Kwiatkowski,
Elizabeth P. Henske

Affiliations

Heng-Jia Liu: Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School
Heng Du: Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School
Damir Khabibullin: Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School
Mahsa Zarei: Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School
Kevin Wei: Division of Rheumatology, Inflammation, and Immunity, Brigham and Women’s Hospital and Harvard Medical School
Gordon J. Freeman: Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School
David J. Kwiatkowski: Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School
Elizabeth P. Henske: Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School

DOI: https://doi.org/10.1038/s41467-023-36881-7
Journal volume & issue: Vol. 14, no. 1
pp. 1 – 22

Abstract

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B7-H3 is expressed at high levels in several cancer types and can suppress antitumor immune responses. Here the authors show that B7-H3 expression is dependent on mTORC1 activity and that inhibition of B7-H3 promotes antitumor immunity mediated by cytolytic CD4 + T cells in tumor models with mTORC1 hyperactivity.

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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