Interleukin-17D promotes lung cancer progression by inducing tumor-associated macrophage infiltration via the p38 MAPK signaling pathway

Abstract

Cancer immunoediting is defined as the integration of the immune system's dual host-protective and tumorpromoting roles, including three phases: elimination, equilibrium, and escape. Immune selective pressure causes tumor cells to lose major histocompatibility complex expression or acquire immunosuppressive gene expression, which promotes tumor immune evasion and tumor progression. Interleukin-17D (IL-17D), a member of the IL-17 family of cytokines, plays an important role in the host defense against infection and inflammation. However, the role of IL-17D in the progression of lung cancer remains unclear. In this study, we found that IL-17D was highly expressed in human lung cancer, and increased IL-17D expression was associated with tumor stage and short overall survival. IL-17D overexpression significantly promoted tumor growth in subcutaneous xenograft mouse models but only slightly affected cell proliferation in vitro. Using flow cytometry, we found that IL-17D overexpression enhances the recruitment of tumor-associated macrophages to the tumor microenvironment. Based on the expression profile of IL17D-overexpressing A549 cells, we found that IL-17D increased the expression levels of macrophage polarization-and recruitmentrelated genes through the MAPK signaling pathway. Moreover, inhibition of the p38 pathway blocked macrophage infiltration induced by IL-17D. These results suggest that IL-17D regulates the tumor immune microenvironment via the p38 MAPK signaling pathway, highlighting IL-17D as a potential therapeutic target for lung cancer.

Notopterol Suppresses IL-17-Induced Proliferation and Invasion of A549 Lung Adenocarcinoma Cells via Modulation of STAT3, NF-κB, and AP-1 Activation

“…The activation of these complex signaling pathways leads to the induction of tumorigenic properties in cancer cells, including the upregulation of proliferation (cyclin D1), invasive (MMP-9, MT1-MMP, uPA, and uPAR), and inflammatory (IL-6 and TNF-α) proteins [13][14][15]. Furthermore, the IL-17-induced epithelial-mesenchymal transition (EMT) promotes metastasis by regulating the NF-κB and MAPK signaling pathways, as reported in previous studies [16][17][18]. The inhibition of IL-17 has been shown to suppress metastasis and improve sensitivity to both chemotherapy and radiation therapy in preclinical cancer models [7].…”

ANKRD49 promotes the metastasis of NCI-H1299 and NCI-H1703 cells via activating JNK-ATF2/c-Jun-MMP-2/9 axis

“…These data demonstrate that the JNK signaling pathway participates in ANKRD49-induced migration and invasion of H1299 and H1703 cells. Activated p38 signaling pathway maybe involved in other processes such as tumor immunity(Lin et al, 2022) rather than metastasis in current settings. The present results were inconsistent with those in A549 cells, a possible reason was that these three types of cell lines have diverse histology and genetic backgrounds.…”

Identification ofPSMD11as a novel cuproptosis‐ and immune‐related prognostic biomarker promoting lung adenocarcinoma progression

“…We utilized the published data from the NCBI GEO database with the accession code GSE148071 15 . By analyzing differentially expressed genes in each cluster, we had previously identified 11 major cell types 16 . The final results were visualized using t‐distributed stochastic neighbor embedding (t‐SNE) for dimensionality reduction.…”