Myeloid-derived suppressor cells promote lung cancer metastasis by CCL11 to activate ERK and AKT signaling and induce epithelial-mesenchymal transition in tumor cells

Oncogene. 2021 Feb;40(8):1476-1489. doi: 10.1038/s41388-020-01605-4. Epub 2021 Jan 15.


Myeloid-derived suppressor cells (MDSCs) suppress antitumor immune activities and facilitate cancer progression. Although the concept of immunosuppressive MDSCs is well established, the mechanism that MDSCs regulate non-small cell lung cancer (NSCLC) progression through the paracrine signals is still lacking. Here, we reported that the infiltration of MDSCs within NSCLC tissues was associated with the progression of cancer status, and was positively correlated with the Patient-derived xenograft model establishment, and poor patient prognosis. Intratumoral MDSCs directly promoted NSCLC metastasis and highly expressed chemokines that promote NSCLC cells invasion, including CCL11. CCL11 was capable of activating the AKT and ERK signaling pathways to promote NSCLC metastasis through the epithelial-mesenchymal transition (EMT) process. Moreover, high expression of CCL11 was associated with a poor prognosis in lung cancer as well as other types of cancer. Our findings underscore that MDSCs produce CCL11 to promote NSCLC metastasis via activation of ERK and AKT signaling and induction of EMT, suggesting that the MDSCs-CCL11-ERK/AKT-EMT axis contains potential targets for NSCLC metastasis treatment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics*
  • Chemokine CCL11 / genetics*
  • Epithelial-Mesenchymal Transition / genetics*
  • Gene Expression Regulation, Neoplastic / genetics
  • Humans
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / pathology
  • MAP Kinase Signaling System / genetics
  • Mice
  • Myeloid-Derived Suppressor Cells / metabolism
  • Myeloid-Derived Suppressor Cells / pathology
  • Neoplasm Metastasis
  • Signal Transduction / genetics
  • Xenograft Model Antitumor Assays


  • CCL11 protein, human
  • Chemokine CCL11