Qntrolling the LncRNA HULC-Tregs-PD-1 axis inhibits immune escape in the tumor microenvironment

Abstract

BackgroundImmune escape remains a major challenge in the treatment of malignant tumors. Here, we studied the mechanisms underlying immune escape in the tumor microenvironment and identified a potential therapeutic target. MethodsPathological specimens from patients with liver cancer, soft tissue sarcoma, and liver metastasis of colon cancer were subjected to immunohistochemistry analysis to detect the expression of programmed death-1 (PD-1) in the tumor microenvironment (TME). Additionally, the expression of regulatory T cells (Tregs) and long non-coding RNAs (lncRNAs), such as highly upregulated in liver cancer (HULC) was evaluated by fluorescence in situ hybridization, and the relationship between HULC, Treg cells, and PD-1 was determined. The animals were divided into H22 hepatic carcinoma and S180 sarcoma groups. Each group was divided into Foxp3−/-C57BL/6J and C57BL/6J mice. Thereafter, mice were inoculated with 0.1 ml S180 sarcoma cells or 0.1 ml H22 hepatoma cells, at a concentration of 1 × 107/ml. The number of splenic CD4+CD25+Foxp3+ T cells was detected by flow cytometry, and serum interleukin-10 (IL-10) and transforming growth factor β1 (TGF-β1) levels were detected using a Luminex liquid suspension chip. Expression of PD-1, fork head box P3 (Foxp3), and HULC in the TME, were analyzed and the therapeutic effect of inhibiting the lncRNA HULC-Treg-PD-1 axis in malignant tumors was determined. ResultsHigh expression of lncRNA HULC promotes the proliferation of Treg cells and increases PD-1 expression in the tumor microenvironment. The HULC-Treg-PD-1 axis plays an immunosuppressive role and promotes the proliferation of malignant tumors. Knocking out the Foxp3 gene can affect the HULC-Treg-PD-1 axis and reduce PD-1, IL-10, and TGF-β1 expression to control the growth of malignant tumors. ConclusionThe lncRNA HULC-Treg-PD-1 axis promotes the growth of malignant tumors. This axis could be modulated to reduce PD-1, IL-10, and TGF-β1 expression and the subsequent immune escape. The inhibition of immune escape in the tumor microenvironment can be achieved by controlling the LncRNA HULC-Treg-PD-1 axis.