IL-22: A key inflammatory mediator as a biomarker and potential therapeutic target for lung cancer

Abstract

Lung cancer, one of the most prevalent cancers worldwide, stands as the primary cause of cancer-related deaths. As is well-known, the utmost crucial risk factor contributing to lung cancer is smoking. In recent years, remarkable progress has been made in treating lung cancer, particularly non-small cell lung cancer (NSCLC). Nevertheless, the absence of effective and accurate biomarkers for diagnosing and treating lung cancer remains a pressing issue. Interleukin 22 (IL-22) is a member of the IL-10 cytokine family. It exerts biological functions (including induction of proliferation and anti-apoptotic signaling pathways, enhancement of tissue regeneration and immunity defense) by binding to heterodimeric receptors containing type 1 receptor chain (R1) and type 2 receptor chain (R2). IL-22 has been identified as a pro-cancer factor since dysregulation of the IL-22-IL-22R system has been implicated in the development of different cancers, including lung, breast, gastric, pancreatic, and colon cancers. In this review, we discuss the differential expression, regulatory role, and potential clinical significance of IL-22 in lung cancer, while shedding light on innovative approaches for the future.

Keywords: Biomarker; IL-22; Inflammation immunology; Lung cancer.

Graphical abstract

Fig. 1

IL-22 plays four main functions during the progression of lung cancer. 1) Promote lung cancer cell proliferation and invasion, and inhibit lung cancer cell apoptosis; 2) Regulate the abundance of immune cells in lung cancer tissues and activate the inflammatory microenvironment; 3) Promote cancer angiogenesis; 4) Activate lung cancer stem cells.

Fig. 2

IL-22 induces NK cells to overexpress CD155, which binds to NK cell activation receptor CD226. Over-activation leads to a decrease in the amount of CD226 and impaired NK cell function, thereby mediating tumor cell immune escape.

Fig. 3

IL-22 promotes the proliferation, migration and epithelial-mesenchymal transition of lung cancer cells through PI3K/AKT, JAK-STAT3, p38 MAPK and other signaling pathways, and antagonizes the apoptosis of lung cancer cells induced by anti-tumor drugs.

Fig. 4

Crispr-cas13-based IL-22 mRNA editing can be utilized for lung cancer therapy by combining with emerging technologies such as single-base editing and single-cell sequencing.

Fig. 5

Precision delivery of various nanomaterials containing IL-22 related drugs for the treatment of lung cancer.