Activation of the GPR35 on ILC2 drives immunosuppression to promote lung cancer progression

Jiawei Yue; Hui Guo; Peng Xu; Jinhong Ma; Yumin Wu

Activation of the GPR35 on ILC2 drives immunosuppression to promote lung cancer progression

Am J Cancer Res. 2023 Jun 15;13(6):2426-2438. eCollection 2023.

Authors

Jiawei Yue¹, Hui Guo², Peng Xu¹, Jinhong Ma², Yumin Wu^{2

3}

Affiliations

¹ Department of Orthopaedics, The Third Affiliated Hospital of Soochow University Changzhou 213003, Jiangsu, China.
² Department of Laboratory Medicine, The Third Affiliated Hospital of Soochow University Changzhou 213003, Jiangsu, China.
³ Jiangsu Key Laboratory for Carbon-Based Functional Materials and Devices, Institute of Nano and Soft Materials (FUNSOM), College of Nano Science & Technology (CNST) Suzhou 215123, Jiangsu, China.

PMID: 37424810
PMCID: PMC10326596

Abstract

Lung cancer is the most common cancer type with poor prognosis. While G protein-coupled receptor 35 (GPR35) is a potent stimulator of tumor growth, group 2 innate lymphoid cells (ILC2) have shown dual effects in tumorigenesis. Intriguingly, inflammation induced GPR35 activation leads to an upregulation in the markers associated with ILC2. Here, we reported that GPR35 knockout mice exhibited a significantly reduced tumor growth and altered immune infiltration in tumors. Furthermore, activating GPR35 in different mouse models promoted tumor development by enhancing the production of IL-5 and IL-13, thereby facilitating the formation of the ILC2-MDSC axis. Moreover, we found that GPR35 was a poor prognostic factor in patients with lung adenocarcinoma. Together, our findings suggest the potential application of targeting GPR35 in cancer immunotherapy.

Keywords: G protein-coupled receptor 35 (GPR35); group 2 innate lymphoid cells (ILC2); immune infiltration; immune therapies; prognostic factor.