Interleukin-35 as an Emerging Player in Tumor Microenvironment

Xue, Wenhua; Yan, Dan; Kan, Quancheng

The role of IL-35 in promotion and development of cancer is consolidated by Huang et al. in an experimental study. It showed the overexpression of IL-35 in human pancreatic ductal adenocarcinoma (PDAC) and linked it with the poor prognosis of it. It was revealed that IL-35 contributes significantly to extravasation and metastasis by aiding adhesion to endothelial cells via Intracellular Adhesion Molecule-1 (ICAM1) dependent mechanism [60] . Likewise, circulating levels of plasma IL-35 were higher in PDAC along with correlated increase in IL-35 mRNA expression and worsening tumor stage [61] . Elevated levels of IL-35 in bone marrow, peripheral blood plasma and TME of patients with Acute Myeloid Leukemia (AML) are also reported [62] [63] [64] [65] . An important clinical study put forward by Zhao and colleagues described the data from 60 breast invasive ductal carcinoma (IDC) patients and confirmed the presence of robust IL-35 expression in tumor infiltrating lymphocytes (TILs). Higher IL-35 expression was correlated with increased tumor size, advanced age (>50 Years), TNM (Tumor, Node, and Metastases) stage III and lymph node metastasis [66] . Previously, comparable results were presented by another research group working on IL-35 and its link with breast cancer [67] . Same study held low circulating IL-23: IL-35 ratio responsible for poor prognosis of breast cancer. Likewise Hamidinia and group implicated raised number of Treg cells and corresponding increase in IL-35 and other immune suppressor cytokines such as IL-10 and TGF-β in breast cancer patients with different clinical stages [68] . Study was performed on 40 breast cancer patient and complements the earlier reports. Similar tumor promoting results showing direct or indirect involvements of IL-35 in colorectal cancer are also reported [69] . In line with the previous data Yi Lu described IL-35 as an important biomarker in thyroid cancer diagnosis [70] . This data suggests the gross involvement of IL-35 in various types of cancers. Though exact mechanism of action through which IL-35 acts remains elusive, but there is abundant data implicating IL-35 in cancer.