2. Academic Validation
  3. Engagement of MHC class I by the inhibitory receptor LILRB1 suppresses macrophages and is a target of cancer immunotherapy

Engagement of MHC class I by the inhibitory receptor LILRB1 suppresses macrophages and is a target of cancer immunotherapy

  • Nat Immunol. 2018 Jan;19(1):76-84. doi: 10.1038/s41590-017-0004-z.
Amira A Barkal 1,  Kipp Weiskopf 1 2,  Kevin S Kao 1,  Sydney R Gordon 1,  Benyamin Rosental 1,  Ying Y Yiu 1,  Benson M George 1,  Maxim Markovic 1,  Nan G Ring 1,  Jonathan M Tsai 1,  Kelly M McKenna 1,  Po Yi Ho 1,  Robin Z Cheng 1,  James Y Chen 1,  Layla J Barkal 3,  Aaron M Ring 4,  Irving L Weissman 5 6 7 8,  Roy L Maute 9 10
Affiliations

Affiliations

  • 1 Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA, USA.
  • 2 Brigham and Women's Hospital, Boston, MA, USA.
  • 3 Department of Biomedical Engineering, University of Wisconsin-Madison, Madison, WI, USA.
  • 4 Department of Immunobiology, Yale University School of Medicine, New Haven, CT, USA.
  • 5 Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA, USA. irv@stanford.edu.
  • 6 Ludwig Center for Cancer Stem Cell Research and Medicine, Stanford, CA, USA. irv@stanford.edu.
  • 7 Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA, USA. irv@stanford.edu.
  • 8 Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA. irv@stanford.edu.
  • 9 Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA, USA. rmaute@stanford.edu.
  • 10 Ab Initio Biotherapeutics, South San Francisco, CA, USA. rmaute@stanford.edu.
PMID: 29180808 DOI: 10.1038/s41590-017-0004-z
Abstract

Exciting progress in the field of Cancer Immunotherapy has renewed the urgency of the need for basic studies of immunoregulation in both adaptive cell lineages and innate cell lineages. Here we found a central role for major histocompatibility complex (MHC) class I in controlling the phagocytic function of macrophages. Our results demonstrated that expression of the common MHC class I component β2-microglobulin (β2M) by Cancer cells directly protected them from phagocytosis. We further showed that this protection was mediated by the inhibitory receptor LILRB1, whose expression was upregulated on the surface of macrophages, including tumor-associated macrophages. Disruption of either MHC class I or LILRB1 potentiated phagocytosis of tumor cells both in vitro and in vivo, which defines the MHC class I-LILRB1 signaling axis as an important regulator of the effector function of innate immune cells, a potential biomarker for therapeutic response to agents directed against the signal-regulatory protein CD47 and a potential target of anti-cancer immunotherapy.

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