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Tumor-associated neutrophils activated by tumor-derived CCL20 (C-C motif chemokine ligand 20) promote T cell immunosuppression via programmed death-ligand 1 (PD-L1) in breast cancer.
Kwantwi, Louis Boafo; Wang, Shujing; Zhang, Wenjun; Peng, Weidong; Cai, Zeyu; Sheng, Youjing; Xiao, Han; Wang, Xian; Wu, Qiang.
Afiliação
  • Kwantwi LB; Department of Pathology, School of Basic Medical Science, Anhui Medical University, Hefei, PR China.
  • Wang S; Department of Immunology, School of Basic Medical Science, Anhui Medical University, Hefei, PR China.
  • Zhang W; Department of Pathology, School of Basic Medical Science, Anhui Medical University, Hefei, PR China.
  • Peng W; Department of Pathology, School of Basic Medical Science, Anhui Medical University, Hefei, PR China.
  • Cai Z; Department of Pathology, School of Basic Medical Science, Anhui Medical University, Hefei, PR China.
  • Sheng Y; Department of Pathology, School of Basic Medical Science, Anhui Medical University, Hefei, PR China.
  • Xiao H; Department of Pathology, The First Affiliated Hospital of Anhui Medical University, Hefei, PR China.
  • Wang X; Department of Pathology, The Second Affiliated Hospital of Anhui Medical University, Hefei, PR China.
  • Wu Q; Department of Pathology, School of Basic Medical Science, Anhui Medical University, Hefei, PR China.
Bioengineered ; 12(1): 6996-7006, 2021 12.
Article em En | MEDLINE | ID: mdl-34519637
ABSTRACT
Breast cancer is the leading cause of cancer-related death among women despite the significant improvement in diagnosis and treatment. Tumor-associated neutrophils have been shown to suppress antitumor functions of the host. However, how breast cancer tumor microenvironment influences the phenotype and functions of neutrophils to potentiate T cell immunosuppression is unknown. Herein, neutrophils isolated from peripheral blood of healthy donors were treated with supernatants from breast cancer cell lines or recombinant human CCL20. PD-L1 expression on neutrophils was then evaluated by immunofluorescence and flow cytometry. Neutrophils and Jurkat T cells were cocultured to evaluate the effect of tumor-associated neutrophils on T cell functions. Finally, immunohistochemical staining was performed to evaluate the clinical relevance of neutrophils infiltrating breast tumor tissues. Tumor-derived CCL20 activated and upregulated PD-L1 expression on neutrophils. A significant positive correlation was found between CCL20 and CD66b+ neutrophils in tumor tissues. Through in vitro experiment, tumor-associated neutrophils (TANs) effectively suppressed T cell immunity which was reversed upon PD-L1 blockade.Moreover, a high density of TANs was associated with short disease free survival in breast cancer patients. Furthermore, receiver operating curve showed that the density of TANs could accurately predict disease-free survival in breast cancer patients. Our findings suggest that targeting TANs via CCL20 immunosuppressive pathway may be a novel therapeutic strategy for breast cancer treatment.
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Texto completo: 1 Coleções: 01-internacional Temas: Geral / Tipos_de_cancer / Outros_tipos Base de dados: MEDLINE Assunto principal: Neoplasias da Mama / Quimiocina CCL20 / Antígeno B7-H1 / Neutrófilos Tipo de estudo: Prognostic_studies / Risk_factors_studies Limite: Female / Humans / Male Idioma: En Revista: Bioengineered Ano de publicação: 2021 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Temas: Geral / Tipos_de_cancer / Outros_tipos Base de dados: MEDLINE Assunto principal: Neoplasias da Mama / Quimiocina CCL20 / Antígeno B7-H1 / Neutrófilos Tipo de estudo: Prognostic_studies / Risk_factors_studies Limite: Female / Humans / Male Idioma: En Revista: Bioengineered Ano de publicação: 2021 Tipo de documento: Article