Hypoxia Induces Overexpression of CCL28 to Recruit Treg Cells to Enhance Angiogenesis in Lung Adenocarcinoma.

Lung cancer is the world-leading causative factor of disease-related death. CD4+CD25+ regulatory T cells (CD4+CD25+ Treg), which are involved in immune escape of tumor cells, are highly related to tumor development and metastasis. Hypoxia induces the overexpression of chemokine (C-C motif) ligand 28 (CCL28), thus enhancing the angiogenesis and metastasis of lung adenocarcinoma. Our study revealed that most clinical lung adenocarcinoma samples showed positive expressions of HIF-lα, VEGF, FoxP3, and CCL28. More CD4+CD25+ Treg cells were detected in the cancerous samples. In addition, hypoxia increased the expression of HIF-1α and upregulated CCL28 to recruit CD4+CD25+ Treg cells; knockdown of HIF-1α could reverse this process. Treg cells also promoted invasion, migration, and angiogenesis in two human lung adenocarcinoma cell lines A549 and H1975. Our study suggested a novel potential molecular mechanism involved in the progression of lung adenocarcinoma could be a potential therapeutic target for the treatment of lung cancer.