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Proc Natl Acad Sci U S A. 2015 Feb 17;112(7):2145-50. doi: 10.1073/pnas.1424907112. Epub 2015 Feb 2.

Macrophages eat cancer cells using their own calreticulin as a guide: roles of TLR and Btk.

Author information

1
Institute for Stem Cell Biology and Regenerative Medicine, Ludwig Center for Cancer Stem Cell Research and Medicine, Stanford Cancer Institute, and.
2
Institute for Stem Cell Biology and Regenerative Medicine.
3
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.

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.

KEYWORDS:

Bruton's tyrosine kinase; Toll-like receptor; immunosurveillance; programmed cell removal; “eat me” signal

PMID:
25646432
PMCID:
PMC4343163
DOI:
10.1073/pnas.1424907112
[Indexed for MEDLINE]
Free PMC Article

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