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

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

  • Breast Cancer. 2023 May 13. doi: 10.1007/s12282-023-01467-0.
Freeha Khalid 1,  Kiyoshi Takagi 2,  Ai Sato 3,  Mio Yamaguchi 3,  Fouzia Guestini 1,  Yasuhiro Miki 4,  Minoru Miyashita 5,  Hisashi Hirakawa 6 7,  Yasuyo Ohi 8,  Yoshiaki Rai 9,  Yasuaki Sagara 9,  Hironobu Sasano 1,  Takashi Suzuki 1 3 10
Affiliations

Affiliations

  • 1 Department of Anatomic Pathology, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi, 980-8575, Japan.
  • 2 Department of Pathology and Histotechnology, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi, 980-8575, Japan. kiyoshi.takagi.b7@tohoku.ac.jp.
  • 3 Department of Pathology and Histotechnology, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi, 980-8575, Japan.
  • 4 Department of Nursing, Faculty of Medical Science and Welfare, Tohoku Bunka Gakuen University, 6-45-1 Kunimi, Aoba-ku, Sendai, Miyagi, 981-8551, Japan.
  • 5 Department of Breast and Endocrine Surgical Oncology, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi, 980-8575, Japan.
  • 6 Department of Surgery, Japan Community Health Care Organization Sendai Hospital, 2-1-1 Murasakiyama, Izumi-ku, Sendai, 981-3281, Japan.
  • 7 Department of Surgery, Tohoku Kosai Hospital, 2-3-11 Kokubun-cho, Aoba-ku, Sendai, Miyagi, 980-0803, Japan.
  • 8 Department of Pathology, Hakuaikai Sagara Hospital, 3-31 Matsubara-machi, Kagoshima, 892-0833, Japan.
  • 9 Department of Breast Surgical Oncology, Hakuaikai Sagara Hospital, 3-31 Matsubara-machi, Kagoshima, 892-0833, Japan.
  • 10 Department of Pathology, Tohoku University Hospital, 1-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi, 980-8574, Japan.
PMID: 37178415 DOI: 10.1007/s12282-023-01467-0
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.

Keywords

IL-17A; Neutrophil; Prognostic factor; TNBC; Tumor microenvironment.

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