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13.05.2023 | Original Article

Interleukin (IL)-17A in triple-negative breast cancer: a potent prognostic factor associated with intratumoral neutrophil infiltration

verfasst von: Freeha Khalid, Kiyoshi Takagi, Ai Sato, Mio Yamaguchi, Fouzia Guestini, Yasuhiro Miki, Minoru Miyashita, Hisashi Hirakawa, Yasuyo Ohi, Yoshiaki Rai, Yasuaki Sagara, Hironobu Sasano, Takashi Suzuki

Erschienen in: Breast Cancer | Ausgabe 5/2023

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Abstract

Background

Triple-negative breast cancer (TNBC) is characterized as highly immunogenic and lacks specific targeted therapies. Interleukin 17A (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 recruitments of neutrophil into tumor tissues. Although IL-17A is considered tumor-promoting in breast cancer, its significance in the possible regulation of neutrophil infiltration in TNBC is not clearly defined.

Materials and methods

We immunolocalized IL-17A, CD66b (neutrophil marker), and chemokine (C-X-C motif) ligand 1 (CXCL1, neutrophil chemoattractant) in 108 TNBC specimens and assessed their correlation among each other. The correlation between these markers and clinicopathological parameters was also assessed. We subsequently performed in vitro study to address the possible regulation of CXCL1 by IL-17A using TNBC cell lines, MDA-MB-231 and HCC-38.

Results

It was revealed that IL-17A correlated significantly with CXCL1 and CD66b, also CD66b with CXCL1. Furthermore, IL-17A was significantly associated with shorter disease-free and overall survival, 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 this induction was significantly suppressed by an Akt inhibitor.

Conclusion

IL-17A was considered to contribute to neutrophil infiltration by inducing CXCL1 in TNBC tissues and educating neutrophils to promote tumor progression. IL-17A might therefore serve as a potent prognostic factor in TNBC.

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Titel: Interleukin (IL)-17A in triple-negative breast cancer: a potent prognostic factor associated with intratumoral neutrophil infiltration
verfasst von: Freeha Khalid
Kiyoshi Takagi
Ai Sato
Mio Yamaguchi
Fouzia Guestini
Yasuhiro Miki
Minoru Miyashita
Hisashi Hirakawa
Yasuyo Ohi
Yoshiaki Rai
Yasuaki Sagara
Hironobu Sasano
Takashi Suzuki
Publikationsdatum: 13.05.2023
Verlag: Springer Nature Singapore
Erschienen in: Breast Cancer / Ausgabe 5/2023
Print ISSN: 1340-6868
Elektronische ISSN: 1880-4233
DOI: https://doi.org/10.1007/s12282-023-01467-0

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Interleukin (IL)-17A in triple-negative breast cancer: a potent prognostic factor associated with intratumoral neutrophil infiltration