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Br J Cancer. 2015 Apr 28;112(9):1501-9. doi: 10.1038/bjc.2015.101. Epub 2015 Mar 31.

IFN-γ from lymphocytes induces PD-L1 expression and promotes progression of ovarian cancer.

Author information

1
Department of Gynecology and Obstetrics, Kyoto University Graduate School of Medicine, 54 Shogoin Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan.
2
Department of Obstetrics and Gynecology, Faculty of Medicine, Kinki University, 377-2 Onohigashi, Osakasayama, Osaka 589-0014, Japan.

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.

PMID:
25867264
PMCID:
PMC4453666
DOI:
10.1038/bjc.2015.101
[Indexed for MEDLINE]
Free PMC Article

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