Title | Engagement of MHC class I by the inhibitory receptor LILRB1 suppresses macrophages and is a target of cancer immunotherapy. |
Publication Type | Journal Article |
Year of Publication | 2018 |
Authors | Barkal AA, Weiskopf K, Kao KS, Gordon SR, Rosental B, Yiu YY, George BM, Markovic M, Ring NG, Tsai JM, McKenna KM, Ho PYi, Cheng RZ, Chen JY, Barkal LJ, Ring AM, Weissman IL, Maute RL |
Journal | Nat Immunol |
Volume | 19 |
Issue | 1 |
Pagination | 76-84 |
Date Published | 2018 Jan |
ISSN | 1529-2916 |
Keywords | Animals, Cell Line, Tumor, Histocompatibility Antigens Class I, Humans, Immunotherapy, Leukocyte Immunoglobulin-like Receptor B1, Macrophages, Mice, Inbred BALB C, Mice, Inbred C57BL, Mice, Inbred NOD, Mice, Knockout, Mice, SCID, Neoplasms, Neoplasms, Experimental, Phagocytosis |
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 β-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. |
DOI | 10.1038/s41590-017-0004-z |
Alternate Journal | Nat. Immunol. |
PubMed ID | 29180808 |
PubMed Central ID | PMC5832354 |
Grant List | T32 GM007365 / GM / NIGMS NIH HHS / United States T32 CA009302 / CA / NCI NIH HHS / United States T32 GM008692 / GM / NIGMS NIH HHS / United States R01 CA086017 / CA / NCI NIH HHS / United States F30 CA232472 / CA / NCI NIH HHS / United States R01 GM100315 / GM / NIGMS NIH HHS / United States F30 DK108561 / DK / NIDDK NIH HHS / United States T32 HL120824 / HL / NHLBI NIH HHS / United States |
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