Macrophages Eat Cancer Cells Using Their Own Calreticulin As a Guide: Roles of TLR and Btk

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2015 Feb 4

PMID 25646432

Citations 144

Authors

Mingye Feng

James Y Chen

Rachel Weissman-Tsukamoto

Jens-Peter Volkmer

Po Yi Ho

Kelly M McKenna

Samuel Cheshier

Michael Zhang

Nan Guo

Phung Gip

Siddhartha S Mitra

Irving L Weissman

Affiliations

Soon will be listed here.

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.

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