Interleukin-35 as an Emerging Player in Tumor Microenvironment

Xue, Wenhua; Yan, Dan; Kan, Quancheng

One of the more recent clinical evidence is put forward by Zhou et al. which showed that plasma level of IL-35 correlates with the progression and metastasis of prostate cancer and that it is independent predictor of the same [53] . An important study implicating IL-35 in prostate cancer is presented by Olson et al. in which authors presented a novel "population of CD8 + CTLA-4 + IL-35-secreting tumor antigen-specific regulatory T cells" and it can affect the antigen-specific effectors responses via an IL-35 dependent mechanism [54] . Another authentication came from recent Wang K et al. study consisting of blood samples from 50 untreated gastric cancer patients, which showed significant upregulation of IL-35 producing B cells [55] . In the research of Pylayeva-Gupta's group, they use a mouse model of pancreatic cancer demonstrated that IL-35+ Bregs are directly recruited to the tumor cell vicinity via a chemokine gradient of CXCL13 and promote tumorigenesis in IL-35 dependent manner [56, 57] . More recently it is pointed that the inhibitory cytokines like IL-35 and TGF-β play a significant role in immune escape of lung cancer cells. Same study confirmed the earlier reports that Foxp3 is an upstream regulator of IL-35 release [58] . Moreover, a clinical study consisting of 106 non-small cell lung cancer (NSCLC) patients and 78 healthy controls discovered a positive correlation between tumor TNM stage, lymph node metastases and circulating levels of IL-35. Inverse relationship between IL-35 and overall survival rate was also found [59] .