CXCL5 as Regulator of Neutrophil Function in Cutaneous Melanoma.

The Journal of Investigative Dermatology
Agnes ForsthuberRobert Loewe

Abstract

Chemokines mold the tumor microenvironment by recruiting distinct immune cell populations, thereby strongly influencing disease progression. Previously, we showed that CXCL5 expression is upregulated in advanced stages of primary melanomas, which correlates with the presence of neutrophils in the tumor. The analysis of neutrophil populations in various tissues revealed a distinct phenotype of tumor-associated neutrophils. Tumor-associated neutrophils expressed PD-L1, CXCR4, CCR5, Adam17, and Nos2 and were immunosuppressive in a T-cell proliferation assay. To investigate the impact of CXCL5 and neutrophils in vivo, we established a syngeneic mouse tumor transplantation model using CXCL5-overexpressing and control melanoma cell lines. Growth behavior or vascularization of primary tumors was not affected by CXCL5 expression and neutrophils alone. However, in combination with Poly(I:C), tumor-associated neutrophils were able to attenuate induced antitumoral T-cell responses. CXCL5-overexpressing tumors had reduced lung metastasis compared with control tumors. Neutrophil depletion reversed this effect. In vitro, unstimulated lung-derived neutrophils had higher levels of reactive oxygen species compared with tumor-associated neutroph...Continue Reading

Citations

Mar 16, 2019·International Journal of Cancer. Journal International Du Cancer·Ziqian LiJun Du
Dec 1, 2019·Experimental Dermatology·Julia Escandon Brehm, Barbara Bedogni
Apr 5, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Bernardo L RapoportRonald Anderson
Jan 29, 2021·Expert Review of Anticancer Therapy·Jun WangQueqiao Bian
Jan 10, 2021·Cancers·Marcin DomagalaMary Poupot
Feb 16, 2021·Frontiers in Oncology·Jia-An ZhangKun Chen
Aug 28, 2020·Cell Reports·Debangshu SamantaGregg L Semenza
Mar 19, 2021·Frontiers in Genetics·Shougang LiuYongfeng Chen
Jul 2, 2021·Journal of Oncology·Xingqing JiaWujun Xiong

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