Interleukin (IL)-17A is a potent prognostic factor associated with intratumoral neutrophil infiltration and C-X-C chemokine motif ligand 1 in triple-negative breast cancer

概要

Triple-negative breast cancer (TNBC) is characterized as highly immunogenic and lacks specific targeted therapies.
Interleukin 17 (IL-17A) is a controversial cytokine and is known to have anti-tumor and pro-tumor roles depending on
the tumor microenvironment. In addition, IL-17A has been recently implicated in the recruitment of neutrophil into
tumor tissues. Although IL-17A is considered as tumor promoting in breast cancer, its significance in possible
regulation of neutrophil infiltration in TNBC is not clearly defined. In this study, we immunolocalized IL-17A,
neutrophils (CD66b) and chemokine (C-X-C motif) ligand 1 (CXCL1), a neutrophil chemoattractant including IL-17A
receptors IL-17RA and IL-17RC in 108 TNBC specimens and assessed their correlation among each other and with
clinicopathological characteristics. Furthermore, we performed in vitro study in order to address the possible
regulation of CXCL1 and activation of oncogenic pathways activated by IL-17A using TNBC cell lines,
MDA-MB-231 and HCC-38.
It was revealed that IL-17A correlated significantly with CXCL1 and CD66b, also CD66b with CXCL1. IL-17A was
significantly associated with poor disease-free and overall survival of the patients, also IL-17A correlated with worse
outcomes especially in a high density CD66b group of patients. In vitro results revealed that IL-17A upregulated
CXCL1 mRNA expression in a dose and time dependent manner and activated Akt pathway, whereas this induction of
CXCL1 was significantly suppressed by Akt inhibitor.
In conclusion, IL-17A was considered to contribute to neutrophil infiltration by inducing CXCL1 in TNBC tissues and
educate neutrophils to promote tumor progression. IL-17A might therefore serve as a poor prognostic factor in TNBC
patients and is responsible for the development of tumor through activating Akt pathway by regulating CXCL1. ...