IDO1 Promotes the Progression of NSCLC by Regulating the Polarization of M2 Macrophages

Xiao Chen; Jie Yao; Meng-Yu Zhang; Rui Li; Xiao Liu; Yi-Qing Qu

doi:10.2147/IJGM.S398908

IDO1 Promotes the Progression of NSCLC by Regulating the Polarization of M2 Macrophages

Int J Gen Med. 2023 May 8:16:1713-1733. doi: 10.2147/IJGM.S398908. eCollection 2023.

Authors

Xiao Chen^{1

2}, Jie Yao¹, Meng-Yu Zhang¹, Rui Li¹, Xiao Liu¹, Yi-Qing Qu¹

Affiliations

¹ Department of Pulmonary and Critical Care Medicine, Qilu Hospital of Shandong University, Jinan, People's Republic of China.
² Department of Respiratory Medicine, Tai'an City Central Hospital, Tai'an, People's Republic of China.

Abstract

Purpose: Non-small cell lung cancer (NSCLC) is currently a problem in the clinic and in society. Tumor-related macrophages (TAMs) in the tumor microenvironment (TME) play a vital role in the development of NSCLC.

Patients and methods: Bioinformatics was used to analyze the role of Indoleamine 2,3-dioxygenase 1 (IDO1) in NSCLC and the correlation of its expression with CD163 expression. The expression of CD163 and IDO1 was measured by immunohistochemistry, and their colocalization was assessed by immunofluorescence. M2 macrophage polarization was induced, and a coculture model of NSCLC cells and macrophages was established.

Results: Bioinformatics analysis showed that IDO1 promoted the metastasis and differentiation of NSCLC and inhibited DNA repair. Moreover, the expression of IDO1 was positively correlated with CD163 expression. We discovered that IDO1 expression was related to M2 macrophage differentiation. In vitro, we showed that increased IDO1 expression promoted the invasion, proliferation, and metastasis of NSCLC cells.

Conclusion: In conclusion, we determined that IDO1 can regulate the M2 polarization of TAMs and promote the progression of NSCLC, which provides partial theoretical evidence for the use of IDO1 inhibitors in the treatment of NSCLC.

Keywords: IDO1; M2 macrophage; NSCLC; TAM; bioinformatics.

Grants and funding

This work was supported by grants from the Major Scientific and Technological Innovation Project of Shandong Province (2018CXGC1212), the CSCO-Qilu Cancer Research Fund (Y-Q201802-014), the Medical and Health Technology Innovation Plan of Jinan City (201805002), the traditional Chinese medicine science and technology project of Shandong Province (2021Q021).