Tumor Cells Interleukin-22 Expression Associates With Elevated Tumor-Associated Macrophages Infiltrating And Poor Prognosis In Patients With Breast Cancer

Interleukin-22 (IL-22) is identified as a tumor-promoting factor in certain cancers, which was secreted by tumor infiltrated lymphocytes. However, the role of IL-22 in breast cancer remains conflicting. In this study, we assessed the expression of IL-22, IL-22 receptor 1 (IL-22R1), CD4, CD8, FOXP3, and CD68 in breast cancer by immunohistochemistry. IL-22 expression was exhibited in 105 (69.1%) cases in tumor cells (tIL-22), whereas only 24 (15.8%) samples displayed IL-22 expression in stromal cells. Multivariate analysis showed that tIL-22 expression was a poor prognostic factor for overall survival (OS) (p = 0.04). Meanwhile, IL-22R1 was predominantly presented in tumor cells (84.9%), which was associated with tIL-22 expression. The CD68-positive tumor-associated macrophages (TAMs) displayed the highest infiltration rate (50.7%) compared with CD4(-), CD8(-), and FOXP3-positive cells. Kaplan-Meier analysis confirmed patients with high TAM infiltration displayed significantly worse relapse-free survival (RFS) compared with low TAMs group (p = 0.017). TAM infiltration was also positively associated with tIL-22 and IL-22R1 expression. Furthermore, tIL-22 expression together with high TAM infiltration displayed the worst prognosis outcomes both in OS (p = 0.039) and RFS (p = 0.008). Instead of lymphocytes, our data indicated that tumor cells express IL-22 in breast cancer that is associated with IL-22R1, high TAM infiltrating, and poor prognosis.