2. Academic Validation
  3. Targeting polarized phenotype of microglia via IL6/JAK2/STAT3 signaling to reduce NSCLC brain metastasis

Targeting polarized phenotype of microglia via IL6/JAK2/STAT3 signaling to reduce NSCLC brain metastasis

  • Signal Transduct Target Ther. 2022 Feb 23;7(1):52. doi: 10.1038/s41392-022-00872-9.
Yu Jin  # 1,  Yalin Kang  # 1,  Minghuan Wang  # 2,  Bili Wu 1,  Beibei Su 1,  Han Yin 1,  Yang Tang 1,  Qianxia Li 1,  Wenjie Wei 1,  Qi Mei 1,  Guangyuan Hu 1,  Veronika Lukacs-Kornek 3,  Jian Li 3,  Kongming Wu 1,  Xianglin Yuan 4,  Wei Wang 5
Affiliations

Affiliations

  • 1 Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei Province, China.
  • 2 Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei Province, China.
  • 3 Institute of Experimental Immunology, University Clinic of Rheinische Friedrich-Wilhelms-University, Bonn, Germany.
  • 4 Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei Province, China. yuanxianglin@hust.edu.cn.
  • 5 Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei Province, China. wwang@vip.126.com.
  • # Contributed equally.
PMID: 35194016 DOI: 10.1038/s41392-022-00872-9
Abstract

Tumor-associated macrophages have emerged as crucial factors for metastases. Microglia are indispensable components of the brain microenvironment and play vital roles in brain metastasis (BM). However, the underlying mechanism of how activated microglia promote brain metastasis of non-small cell lung Cancer (NSCLC) remains elusive. Here, we purified cell lines with brain-metastatic tropism and employed a co-culture system to reveal their communication with microglia. By single-cell RNA-sequencing and transcriptome difference analysis, we identified IL6 as the key regulator in brain-metastatic cells (A549-F3) to induce anti-inflammatory microglia via JAK2/STAT3 signaling, which in turn promoted the colonization process in metastatic A549-F3 cells. In our clinical samples, patients with higher levels of IL6 in serum showed higher propensity for brain metastasis. Additionally, the TCGA (The Cancer Genome Atlas) data revealed that NSCLC patients with a lower level of IL6 had a longer overall survival time compared to those with a higher level of IL6. Overall, our data indicate that the targeting of IL6/JAK2/STAT3 signaling in activated microglia may be a promising new approach for inhibiting brain metastasis in NSCLC patients.

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