Mechanism of immune escape mediated by receptor tyrosine kinase KIT in thyroid cancer

Thyroid cancer (TC) is one of the fastest-growing malignant tumors. This study sought to explore the mechanism of immune escape mediated by receptor tyrosine kinase (KIT) in TC.

The expression microarray of TC was acquired through the GEO database, and the difference analysis and Kyoto encyclopedia of genes and genomes pathway enrichment analysis were carried out. KIT levels in TC cell lines (K1/SW579/BCPAP) and human normal thyroid cells were detected using reverse transcription quantitative polymerase chain reaction and western blot analysis. TC cells were transfected with overexpressed (oe)-KIT and CD8+ T cells were cocultured with SW579 cells. Subsequently, cell proliferation, migration, and invasion abilities, CD8+ T cell proliferation, cytokine levels (interferon-γ [IFN-γ]/tumor necrosis factor-α [TNF-α]) were determined using colony formation assay, Transwell assays, flow cytometry, and enzyme-linked immunosorbent assay. The phosphorylation of MAPK pathway-related protein (ERK) was measured by western blot analysis. After transfection with oe-KIT, cells were treated with anisomycin (an activator of the MAPK pathway), and the protein levels of p-ERK/ERK and programmed death-ligand 1 (PD-L1) were detected.

Differentially expressed genes (N = 2472) were obtained from the GEO database. KIT was reduced in TC samples and lower in tumor cells than those in normal cells. Overexpression of KIT inhibited immune escape of TC cells. Specifically, the proliferation, migration, and invasion abilities of TC cells were lowered, the proliferation level of CD8+ T cells was elevated, and IFN-γ and TNF-α levels were increased. KIT inhibited the activation of the MAPK pathway in TC cells and downregulated PD-L1.

KIT suppressed immune escape of TC by blocking the activation of the MAPK pathway and downregulating PD-L1.