Hydroxychloroquine can impair tumor response to anti-PD1 in subcutaneous mouse models

Simon Wabitsch; John C. McVey; Chi Ma; Benjamin Ruf; Olena Kamenyeva; Justin D. McCallen; Laurence P. Diggs; Bernd Heinrich; Tim F. Greten

iScience (Jan 2021)

Hydroxychloroquine can impair tumor response to anti-PD1 in subcutaneous mouse models

Simon Wabitsch,
John C. McVey,
Chi Ma,
Benjamin Ruf,
Olena Kamenyeva,
Justin D. McCallen,
Laurence P. Diggs,
Bernd Heinrich,
Tim F. Greten

Affiliations

Simon Wabitsch: Gastrointestinal Malignancy Section, Thoracic and GI Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, 9000 Rockville Pike, 10/3B43, Bethesda, MD 20892, USA
John C. McVey: Gastrointestinal Malignancy Section, Thoracic and GI Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, 9000 Rockville Pike, 10/3B43, Bethesda, MD 20892, USA; Cleveland Clinic Lerner College of Medicine at Case Western Reserve University, Cleveland, OH, USA
Chi Ma: Gastrointestinal Malignancy Section, Thoracic and GI Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, 9000 Rockville Pike, 10/3B43, Bethesda, MD 20892, USA
Benjamin Ruf: Gastrointestinal Malignancy Section, Thoracic and GI Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, 9000 Rockville Pike, 10/3B43, Bethesda, MD 20892, USA
Olena Kamenyeva: Biological Imaging Section, Research Technology Branch, National Institute of Allergy and Infectious Diseases, Bethesda, MD, USA
Justin D. McCallen: Gastrointestinal Malignancy Section, Thoracic and GI Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, 9000 Rockville Pike, 10/3B43, Bethesda, MD 20892, USA
Laurence P. Diggs: Gastrointestinal Malignancy Section, Thoracic and GI Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, 9000 Rockville Pike, 10/3B43, Bethesda, MD 20892, USA
Bernd Heinrich: Gastrointestinal Malignancy Section, Thoracic and GI Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, 9000 Rockville Pike, 10/3B43, Bethesda, MD 20892, USA
Tim F. Greten: Gastrointestinal Malignancy Section, Thoracic and GI Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, 9000 Rockville Pike, 10/3B43, Bethesda, MD 20892, USA; Corresponding author

Journal volume & issue: Vol. 24, no. 1
p. 101990

Abstract

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Summary: Hydroxychloroquine (HCQ) is a well-known anti-inflammatory drug but is also known as an anti-inflammatory drug. Here, we evaluate the influence of HCQ treatment on the effect of anti-PD1 tumor immunotherapy. Anti-PD1 therapy-sensitive tumor lines MC38, CT26, and RIL-175 were used to investigate the impact of HCQ on anti-PD1 therapy efficacy. In vitro assays demonstrated that HCQ directly inhibited tumor cell growth in all the tested tumor cell lines. HCQ treatment impaired both antigen-specific and nonspecific T-cell production of TNFα and IFNγ in vitro and in vivo. Importantly, in all the three tumor models, HCQ treatment significantly impaired the response to anti-PD1 treatment, accompanying diminished in vivo T-cell activation and reduced tumor-infiltrating, antigen-specific CD8+ T cells. This study shows that HCQ treatment can result in immunotherapy failure due to its immunosuppressive effects that offset both increased MHC-I expression by tumor cell and direct cytotoxicity.

Published in iScience

ISSN: 2589-0042 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Science
Website: http://www.cell.com/iscience/home

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