Spi-B Promotes the Recruitment of Tumor-Associated Macrophages via Enhancing CCL4 Expression in Lung Cancer

Abstract

Tumor immune escape plays a critical role in malignant tumor progression and leads to the failure of anticancer immunotherapy. Spi-B, a lymphocyte lineage-specific Ets transcription factor, participates in mesenchymal invasion and favors metastasis in human lung cancer. However, the mechanism through which Spi-B regulates the tumor immune environment has not been elucidated. In this study, we demonstrated that Spi-B enhanced the infiltration of tumor-associated macrophages (TAMs) in the tumor microenvironment using subcutaneous mouse models and clinical samples of human lung cancer. Spi-B overexpression increased the expression of TAM polarization- and recruitment-related genes, including <i>CCL4</i>. Moreover, deleting <i>CCL4</i> inhibited the ability of Spi-B promoting macrophage infiltration. These data suggest that Spi-B promotes the recruitment of TAMs to the tumor microenvironment <i>via</i> upregulating <i>CCL4</i> expression, which contributes to the progression of lung cancer.