論文 - 詳細
RRC ID | 36961 |
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著者 | Abiko K, Matsumura N, Hamanishi J, Horikawa N, Murakami R, Yamaguchi K, Yoshioka Y, Baba T, Konishi I, Mandai M. |
タイトル | IFN-γ from lymphocytes induces PD-L1 expression and promotes progression of ovarian cancer. |
ジャーナル | Br J Cancer |
Abstract |
BACKGROUND:PD-L1 (programmed cell death 1 ligand 1) on tumour cells suppresses host immunity through binding to its receptor PD-1 on lymphocytes, and promotes peritoneal dissemination in mouse models of ovarian cancer. However, how PD-L1 expression is regulated in ovarian cancer microenvironment remains unclear. METHODS:The number of CD8-positive lymphocytes and PD-L1 expression in tumour cells was assessed in ovarian cancer clinical samples. PD-L1 expression and tumour progression in mouse models under conditions of altering IFN-γ signals was assessed. RESULTS:The number of CD8-positive cells in cancer stroma was very high in peritoneally disseminated tumours, and was strongly correlated to PD-L1 expression on the tumour cells (P<0.001). In mouse models, depleting IFNGR1 (interferon-γ receptor 1) resulted in lower level of PD-L1 expression in tumour cells, increased the number of tumour-infiltrating CD8-positive lymphocytes, inhibition of peritoneal disseminated tumour growth and longer survival (P=0.02). The injection of IFN-γ into subcutaneous tumours induced PD-L1 expression and promoted tumour growth, and PD-L1 depletion completely abrogated tumour growth caused by IFN-γ injection (P=0.01). CONCLUSIONS:Interferon-γ secreted by CD8-positive lymphocytes upregulates PD-L1 on ovarian cancer cells and promotes tumour growth. The lymphocyte infiltration and the IFN-γ status may be the key to effective anti-PD-1 or anti-PD-L1 therapy in ovarian cancer. |
巻・号 | 112(9) |
ページ | 1501-9 |
公開日 | 2015-4-28 |
DOI | 10.1038/bjc.2015.101 |
PII | bjc2015101 |
PMID | 25867264 |
PMC | PMC4453666 |
MeSH | Animals Apoptosis B7-H1 Antigen / metabolism* Blotting, Western CD8-Positive T-Lymphocytes / drug effects CD8-Positive T-Lymphocytes / immunology* CD8-Positive T-Lymphocytes / pathology Cell Proliferation Disease Progression Female Flow Cytometry Humans Immunoenzyme Techniques Interferon-gamma / pharmacology* Lymphocytes, Tumor-Infiltrating / drug effects Lymphocytes, Tumor-Infiltrating / immunology Lymphocytes, Tumor-Infiltrating / pathology Mice Mice, Inbred C57BL Ovarian Neoplasms / drug therapy Ovarian Neoplasms / immunology Ovarian Neoplasms / metabolism* Ovarian Neoplasms / pathology* Peritoneal Neoplasms / drug therapy Peritoneal Neoplasms / immunology Peritoneal Neoplasms / metabolism* Peritoneal Neoplasms / secondary* Prognosis Tumor Cells, Cultured Tumor Microenvironment / drug effects Up-Regulation Xenograft Model Antitumor Assays |
IF | 5.791 |
引用数 | 257 |
WOS 分野 | ONCOLOGY |
リソース情報 | |
ヒト・動物細胞 | OV2944-HM-1(RCB1483) |