[HTML][HTML] IFN-γ from lymphocytes induces PD-L1 expression and promotes progression of ovarian cancer

K Abiko, N Matsumura, J Hamanishi… - British journal of …, 2015 - nature.com
K Abiko, N Matsumura, J Hamanishi, N Horikawa, R Murakami, K Yamaguchi, Y Yoshioka…
British journal of cancer, 2015nature.com
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 …
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.
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