RRC ID 67491
Author Hangai S, Kawamura T, Kimura Y, Chang CY, Hibino S, Yamamoto D, Nakai Y, Tateishi R, Oshima M, Oshima H, Kodama T, Moriya K, Koike K, Yanai H, Taniguchi T.
Title Orchestration of myeloid-derived suppressor cells in the tumor microenvironment by ubiquitous cellular protein TCTP released by tumor cells.
Journal Nat Immunol
Abstract One of most challenging issues in tumor immunology is a better understanding of the dynamics in the accumulation of myeloid-derived suppressor cells (MDSCs) in the tumor microenvironment (TIME), as this would lead to the development of new cancer therapeutics. Here, we show that translationally controlled tumor protein (TCTP) released by dying tumor cells is an immunomodulator crucial to full-blown MDSC accumulation in the TIME. We provide evidence that extracellular TCTP mediates recruitment of the polymorphonuclear MDSC (PMN-MDSC) population in the TIME via activation of Toll-like receptor-2. As further proof of principle, we show that inhibition of TCTP suppresses PMN-MDSC accumulation and tumor growth. In human cancers, we find an elevation of TCTP and an inverse correlation of TCTP gene dosage with antitumor immune signatures and clinical prognosis. This study reveals the hitherto poorly understood mechanism of the MDSC dynamics in the TIME, offering a new rationale for cancer immunotherapy.
Volume 22(8)
Pages 947-957
Published 2021-8-1
DOI 10.1038/s41590-021-00967-5
PII 10.1038/s41590-021-00967-5
PMID 34239121
MeSH Alarmins / genetics Alarmins / metabolism Animals Biomarkers, Tumor / genetics Biomarkers, Tumor / metabolism* Cell Line, Tumor Chemokine CXCL1 / metabolism* Colorectal Neoplasms / immunology* Female HEK293 Cells Humans Immunotherapy Male Mice Mice, Inbred BALB C Mice, Inbred C57BL Mice, Knockout Myeloid-Derived Suppressor Cells / immunology* RAW 264.7 Cells Toll-Like Receptor 2 / immunology* Tumor Microenvironment / immunology* Tumor Protein, Translationally-Controlled 1
IF 20.479
Human and Animal Cells RAW 264(RCB0535) B16F10(RCB2630) 293T(RCB2202)