title: Macrophages eat cancer cells using their own calreticulin as a guide: roles of TLR and Btk.
abstract: Macrophage-mediated programmed cell removal (PrCR) is an important mechanism of eliminating diseased and damaged cells before programmed cell death. The induction of PrCR by eat-me signals on tumor cells is countered by don't-eat-me signals such as CD47, which binds macrophage signal-regulatory protein α to inhibit phagocytosis. Blockade of CD47 on tumor cells leads to phagocytosis by macrophages. Here we demonstrate that the activation of Toll-like receptor (TLR) signaling pathways in macrophages synergizes with blocking CD47 on tumor cells to enhance PrCR. Bruton's tyrosine kinase (Btk) mediates TLR signaling in macrophages. Calreticulin, previously shown to be an eat-me signal on cancer cells, is activated in macrophages for secretion and cell-surface exposure by TLR and Btk to target cancer cells for phagocytosis, even if the cancer cells themselves do not express calreticulin.
authors: Institute for Stem Cell Biology and Regenerative Medicine, Ludwig Center for Cancer Stem Cell Research and Medicine, Stanford Cancer Institute, and.
authors: Mingye
authors: M
authors: Feng
authors: Institute for Stem Cell Biology and Regenerative Medicine, Ludwig Center for Cancer Stem Cell Research and Medicine, Stanford Cancer Institute, and.
authors: James Y
authors: JY
authors: Chen
authors: Institute for Stem Cell Biology and Regenerative Medicine, Ludwig Center for Cancer Stem Cell Research and Medicine, Stanford Cancer Institute, and.
authors: Rachel
authors: R
authors: Weissman-Tsukamoto
authors: Institute for Stem Cell Biology and Regenerative Medicine, Ludwig Center for Cancer Stem Cell Research and Medicine, Stanford Cancer Institute, and.
authors: Jens-Peter
authors: JP
authors: Volkmer
authors: Institute for Stem Cell Biology and Regenerative Medicine, Ludwig Center for Cancer Stem Cell Research and Medicine, Stanford Cancer Institute, and.
authors: Po Yi
authors: PY
authors: Ho
authors: Institute for Stem Cell Biology and Regenerative Medicine, Ludwig Center for Cancer Stem Cell Research and Medicine, Stanford Cancer Institute, and.
authors: Kelly M
authors: KM
authors: McKenna
authors: Institute for Stem Cell Biology and Regenerative Medicine.
authors: Samuel
authors: S
authors: Cheshier
authors: Institute for Stem Cell Biology and Regenerative Medicine.
authors: Michael
authors: M
authors: Zhang
authors: Institute for Stem Cell Biology and Regenerative Medicine, Ludwig Center for Cancer Stem Cell Research and Medicine, Stanford Cancer Institute, and.
authors: Nan
authors: N
authors: Guo
authors: Institute for Stem Cell Biology and Regenerative Medicine, Ludwig Center for Cancer Stem Cell Research and Medicine, Stanford Cancer Institute, and.
authors: Phung
authors: P
authors: Gip
authors: Institute for Stem Cell Biology and Regenerative Medicine.
authors: Siddhartha S
authors: SS
authors: Mitra
authors: Institute for Stem Cell Biology and Regenerative Medicine, Ludwig Center for Cancer Stem Cell Research and Medicine, Stanford Cancer Institute, and Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305 irv@stanford.edu.
authors: Irving L
authors: IL
authors: Weissman
mesh_terms: D000077329:Agammaglobulinaemia Tyrosine Kinase; D037282:Calreticulin / Q000502:physiology*; D006801:Humans; D008264:Macrophages / Q000276:immunology*; D009369:Neoplasms / Q000201:enzymology / Q000378:metabolism / Q000473:pathology*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D051193:Toll-Like Receptors / Q000502:physiology*
chemical_list: D037282:Calreticulin; D051193:Toll-Like Receptors; D011505:Protein-Tyrosine Kinases; D000077329:Agammaglobulinaemia Tyrosine Kinase; C000625949:BTK protein, human
keywords: Bruton's tyrosine kinase; Toll-like receptor; immunosurveillance; programmed cell removal; “eat me” signal
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