Increased interleukin‐35 expression in tumor‐infiltrating lymphocytes correlates with poor prognosis in patients with breast cancer
HighlightsIL‐35 is expressed in tumor‐infiltrating lymphocytes of breast cancer.The expression level of IL‐35 in TILs may be a valuable prognostic factor for IDC.High plasma IL‐35 levels were associated with late TNM stage in IDC.Increased IL‐35+ populations in the TILs may impair antitumor immune response. ABSTRACT Interleukin‐35 (IL‐35) is a recently discovered inhibitory cytokine, which is firstly discovered to be produced by regulatory T cells (Tregs) and proposed as a key effector molecule of Treg function. This study aims to analyze the correlation between IL‐35 expression in tumor‐infiltrating lymphocytes (TILs) of breast cancer tissue and patients' clinical characteristics. Plasma IL‐35 was also determined in 60 patients with breast invasive ductal carcinoma (IDC) and 30 healthy women by enzyme‐linked immunosorbent assay. IL‐35 expression in the tissue specimens was analyzed by immunohistochemistry. It was shown that 39.1%, 43.6% and 17.3% of the 110 patients were absent, weak, and strong IL‐35 expression in the TILs, respectively. Strong IL‐35 expression in TILs was significantly associated with age >50 years, tumor size >2 cm, TNM stage III, and negative ER (All P < 0.05). Patients with elevated IL‐35 expression in TILs had significantly worse progression‐free survival (PFS) and overall survival (OS) than patients with weak or no IL‐35 expression (All P < 0.05). High plasma IL‐35 levels were significantly associated with TNM stage III and lymph node metastasis (All P < 0.05). Plasma IL‐35 level and IL‐35 expression in the TILs of breast cancer tissues may be a valuable biomarker in the development and prognosis of IDC.