BIRC2 Expression Impairs Anti-Cancer Immunity and Immunotherapy Efficacy

Debangshu Samanta; Tina Yi-Ting Huang; Rima Shah; Yongkang Yang; Fan Pan; Gregg L. Semenza

Cell Reports (Aug 2020)

BIRC2 Expression Impairs Anti-Cancer Immunity and Immunotherapy Efficacy

Debangshu Samanta,
Tina Yi-Ting Huang,
Rima Shah,
Yongkang Yang,
Fan Pan,
Gregg L. Semenza

Affiliations

Debangshu Samanta: Johns Hopkins Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Johns Hopkins University School of Medicine, Baltimore, MD, USA
Tina Yi-Ting Huang: Johns Hopkins Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, USA
Rima Shah: Johns Hopkins Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, USA
Yongkang Yang: Johns Hopkins Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Johns Hopkins University School of Medicine, Baltimore, MD, USA
Fan Pan: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Johns Hopkins University School of Medicine, Baltimore, MD, USA
Gregg L. Semenza: Johns Hopkins Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Radiation Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Biological Chemistry, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Corresponding author

Journal volume & issue: Vol. 32, no. 8
p. 108073

Abstract

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Summary: Immune checkpoint blockade (ICB) has led to therapeutic responses in some cancer patients for whom no effective treatment previously existed. ICB acts on T lymphocytes and other immune cells that are inactivated due to checkpoint signals that inhibit their infiltration and function within tumors. But for more than 80% of patients, immunotherapy has not been effective. Here, we demonstrate a cancer-cell-intrinsic mechanism of immune evasion and resistance to ICB mediated by baculoviral IAP repeat-containing 2 (BIRC2). Knockdown of BIRC2 expression in mouse melanoma or breast cancer cells increases expression of the chemokine CXCL9 and impairs tumor growth by increasing the number of intratumoral activated CD8+ T cells and natural killer cells. Administration of anti-CXCL9 neutralizing antibody inhibits the recruitment of CD8+ T cells and natural killer cells to BIRC2-deficient tumors. Most importantly, BIRC2 deficiency dramatically increases the sensitivity of mouse melanoma and breast tumors to anti-CTLA4 and/or anti-PD1 ICB.

Published in Cell Reports

ISSN: 2211-1247 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Science: Biology (General)
Website: http://www.cell.com/cell-reports/home

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Abstract

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