Tumor-associated tissue eosinophilia promotes angiogenesis and metastasis in head and neck squamous cell carcinoma.

ABSTRACT

Eosinophils are terminally differentiated leukocytes that participate in the process of chronic inflammation and allergy and are able to release multiple cytokines into the surrounding tissue environment. Tumor-associated tissue eosinophilia (TATE) is the presence of eosinophils in the tumor or in the neighboring stroma and has been observed in various types of cancer. In head and neck squamous cell carcinoma (HNSCC), the clinical relevance of TATE has not been concluded yet because of the inconsistent results in different studies. In our study, we focus on the prognostic effects of TATE on HNSCC and how TATE can influence tumor behavior and tumor microenvironment. We first showed that in both the TCGA-HNSC cohort and our cohort of patients with HNSCC who had received curative surgery, TATE is correlated with worse overall survival. To investigate the underlying mechanism of how TATE leads to poor clinical outcomes, we showed that activated eosinophils produce a variety of cytokines and chemokines, and activated TATE-derived culture medium promotes tumor migration mainly through CCL2. We also showed that eosinophils are capable of inducing angiogenesis and that HNSCC samples enriched with TATE are highly correlated with tumor angiogenesis. Furthermore, HNSCC enriched with TATE had more aggressive pathological features, including regional lymph node metastasis, perineural invasion, lymphovascular invasion, and tumor growth. Lastly, we showed that HNSCC enriched with TATE is associated with immunosuppressive tumor microenvironment. Taken together, our results suggest that TATE promotes cancer metastasis and angiogenesis which results in a poor clinical outcomes in HNSCC.