RRC ID 38898
Author Peng J, Hamanishi J, Matsumura N, Abiko K, Murat K, Baba T, Yamaguchi K, Horikawa N, Hosoe Y, Murphy SK, Konishi I, Mandai M.
Title Chemotherapy Induces Programmed Cell Death-Ligand 1 Overexpression via the Nuclear Factor-κB to Foster an Immunosuppressive Tumor Microenvironment in Ovarian Cancer.
Journal Cancer Res
Abstract Emerging evidence has highlighted the host immune system in modulating the patient response to chemotherapy, but the mechanism of this modulation remains unclear. The aim of this study was to analyze the effect of chemotherapy on antitumor immunity in the tumor microenvironment of ovarian cancer. Treatment of ovarian cancer cell lines with various chemotherapeutic agents resulted in upregulated expression of MHC class I and programmed cell death 1 ligand 1 (PD-L1) in a NF-κB-dependent manner and suppression of antigen-specific T-cell function in vitro. In a mouse model of ovarian cancer, treatment with paclitaxel increased CD8(+) T-cell infiltration into the tumor site, upregulated PD-L1 expression, and activated NF-κB signaling. In particular, tumor-bearing mice treated with a combination of paclitaxel and a PD-L1/PD-1 signal blockade survived longer than mice treated with paclitaxel alone. In summary, we found that chemotherapy induces local immune suppression in ovarian cancer through NF-κB-mediated PD-L1 upregulation. Thus, a combination of chemotherapy and immunotherapy targeting the PD-L1/PD-1 signaling axis may improve the antitumor response and offers a promising new treatment modality against ovarian cancer.
Volume 75(23)
Pages 5034-45
Published 2015-12-1
DOI 10.1158/0008-5472.CAN-14-3098
PII 0008-5472.CAN-14-3098
PMID 26573793
MeSH Animals Antineoplastic Combined Chemotherapy Protocols / pharmacology* B7-H1 Antigen / antagonists & inhibitors B7-H1 Antigen / biosynthesis* B7-H1 Antigen / genetics B7-H1 Antigen / immunology Capecitabine / administration & dosage Capecitabine / pharmacology Cell Line, Tumor Docetaxel Female Humans Mice NF-kappa B / immunology NF-kappa B / metabolism* Organoplatinum Compounds / administration & dosage Organoplatinum Compounds / pharmacology Ovarian Neoplasms / drug therapy* Ovarian Neoplasms / genetics Ovarian Neoplasms / immunology Ovarian Neoplasms / metabolism Programmed Cell Death 1 Receptor / antagonists & inhibitors Programmed Cell Death 1 Receptor / immunology Taxoids / administration & dosage Taxoids / pharmacology Transcriptome / drug effects Tumor Microenvironment / drug effects Tumor Microenvironment / immunology* Xenograft Model Antitumor Assays
IF 9.727
Times Cited 193
Human and Animal Cells OV2944-HM-1(RCB1483)