LC3-Associated Phagocytosis in Myeloid Cells Promotes Tumor Immune Tolerance.

Autor:	Cunha LD; Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA., Yang M; Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA., Carter R; Department of Oncology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA., Guy C; Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA., Harris L; Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA., Crawford JC; Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA., Quarato G; Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA., Boada-Romero E; Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA., Kalkavan H; Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA., Johnson MDL; Department of Immunobiology, University of Arizona, Tucson, AZ 85724, USA; BIO5 Institute, University of Arizona, Tucson, AZ 85719, USA; Valley Fever Center for Excellence, University of Arizona, Tucson, AZ 85724, USA., Natarajan S; Department of Oncology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA., Turnis ME; Department of Cell and Molecular Biology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA., Finkelstein D; Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA., Opferman JT; Department of Cell and Molecular Biology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA., Gawad C; Department of Oncology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA; Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA., Green DR; Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA. Electronic address: douglas.green@stjude.org.
Jazyk:	angličtina
Zdroj:	Cell [Cell] 2018 Oct 04; Vol. 175 (2), pp. 429-441.e16. Date of Electronic Publication: 2018 Sep 20.
DOI:	10.1016/j.cell.2018.08.061
Abstrakt:	Targeting autophagy in cancer cells and in the tumor microenvironment are current goals of cancer therapy. However, components of canonical autophagy play roles in other biological processes, adding complexity to this goal. One such alternative function of autophagy proteins is LC3-associated phagocytosis (LAP), which functions in phagosome maturation and subsequent signaling events. Here, we show that impairment of LAP in the myeloid compartment, rather than canonical autophagy, induces control of tumor growth by tumor-associated macrophages (TAM) upon phagocytosis of dying tumor cells. Single-cell RNA sequencing (RNA-seq) analysis revealed that defects in LAP induce pro-inflammatory gene expression and trigger STING-mediated type I interferon responses in TAM. We found that the anti-tumor effects of LAP impairment require tumor-infiltrating T cells, dependent upon STING and the type I interferon response. Therefore, autophagy proteins in the myeloid cells of the tumor microenvironment contribute to immune suppression of T lymphocytes by effecting LAP. (Copyright © 2018 Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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