CXCL9 chemokine promotes the progression of human pancreatic adenocarcinoma through STAT3-dependent cytotoxic T lymphocyte suppression
| Autor: | Hao Chen, Zhiqiang Meng, Jian Tang, Lianyu Chen, Ye Li, Chien-Shan Cheng, Zhen Chen, Huifeng Gao |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
STAT3 Transcription Factor
Aging Chemokine medicine.medical_treatment T cell Gene Expression Adenocarcinoma CD8-Positive T-Lymphocytes Lymphocyte Activation Chemokine CXCL9 Immunophenotyping Immunomodulation Mice Immune system Lymphocytes Tumor-Infiltrating stomatognathic system STAT3 activation Cell Line Tumor medicine pancreatic adenocarcinoma Tumor Microenvironment Cytotoxic T cell CXCL10 CD8+ cytotoxic T cells Animals Humans skin and connective tissue diseases biology Chemistry chemokine Cell Biology Immunotherapy Prognosis Recombinant Proteins Pancreatic Neoplasms stomatognathic diseases Disease Models Animal medicine.anatomical_structure CXCL9 biology.protein Cancer research Disease Progression CD8 Research Paper Signal Transduction T-Lymphocytes Cytotoxic |
| Zdroj: | Aging (Albany NY) |
| ISSN: | 1945-4589 |
| Popis: | Chemokines play essential roles in the progression of various human cancers; however, the expression and role of CXC chemokines in pancreatic adenocarcinoma (PAAD) have not yet been identified. The aim of this study is to identify the expression patterns, clinical significance and mechanisms of CXC chemokines in regulating tumour microenvironment of PAAD. Three CXC chemokines, including CXCL5, CXCL9, and CXCL10, were significantly overexpressed in PAAD tissues, which were correlated with the poor survival of the patients. CXCL9/10 was associated with change of immune cell pattern in the tumour microenvironment, and supplementation of CXCL9 in the orthotopic murine PAAD model promoted tumour progression. In particular, CXCL9 reduced the CD8+ cytotoxic T lymphocytes in the tumour microenvironment of PAAD, which could be attributed to the reduced CD8+ T cell proliferation, activation, and secretion of anti-tumour cytokines. In vitro treatment of CXCL9 directly led to the suppression of the proliferation, activation, and secretion of anti-tumour cytokines of isolated CD8+ T cells. Inhibition of STAT3 recovered the CXCL9-inhibited proliferation, activation, and secretion of anti-tumour cytokines of CD8+ T cells. Our study indicates CXCL9 as a potential target of immunotherapy in PAAD treatment by regulating the CD8+ T lymphocytes in the tumour microenvironment. |
| Databáze: | OpenAIRE |
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