Neutrophil Cathepsin G and Tumor Cell RAGE Facilitate Neutrophil Anti-Tumor Cytotoxicity

Ronit Vogt Sionov, Tanya Fainsod-Levi, Tamir Zelter, Lola Polyansky, Christine T. Pham, Zvi Granot

Research output: Contribution to journalArticlepeer-review

21 Scopus citations

Abstract

Neutrophils are a heterogeneous population of myeloid cells which may either promote or hinder tumor growth and progression. Anti-tumor neutrophils have the capacity to kill tumor cells in a contact-dependent manner. However, the molecular mechanisms underlying tumor cell recognition by neutrophils remained unexplored. Tumor cells were shown to express aberrant glycosylation patterns and neutrophils are equipped with receptors capable of recognizing such glycosylations. Accordingly, we hypothesized that the receptor for advanced glycation end products (RAGE) may facilitate neutrophil recognition of tumor cells. Indeed, RAGE decoy receptors and RAGE-specific blocking antibodies dramatically reduce tumor cell susceptibility to neutrophil cytotoxicity. Unexpectedly, we found that tumor cell RAGE rather than neutrophil RAGE is important for the killing process. We further identified neutrophil Cathepsin G as the neutrophil component interacting with tumor cell RAGE. Cathepsin G-deficient neutrophils show impaired ability to kill tumor cells, suggesting that RAGE-Cathepsin G interaction is required for neutrophil cytotoxicity. These data unravel new aspects of neutrophil anti-tumor activity and identify a novel role for RAGE and Cathepsin G in neutrophil-mediated cytotoxicity.

Original languageEnglish
Article numbere1624129
JournalOncoImmunology
Volume8
Issue number9
DOIs
StatePublished - Sep 2 2019

Keywords

  • Cathepsin G
  • RAGE
  • neutrophil cytotoxicity
  • tumor cell killing

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