Orchestration of myeloid-derived suppressor cells in the tumor microenvironment by ubiquitous cellular protein TCTP released by tumor cells

Nat Immunol. 2021 Aug;22(8):947-957. doi: 10.1038/s41590-021-00967-5. Epub 2021 Jul 8.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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


  • Alarmins
  • Biomarkers, Tumor
  • CXCL1 protein, human
  • Chemokine CXCL1
  • TLR2 protein, human
  • TPT1 protein, human
  • Toll-Like Receptor 2
  • Tpt1 protein, mouse
  • Tumor Protein, Translationally-Controlled 1