IFN-γ from lymphocytes induces PD-L1 expression and promotes progression of ovarian cancer
By K. Abiko, N. Matsumura, J. Hamanishi, N. Horikawa, R. Murakami, K. Yamaguchi, Y. Yoshioka, T. Baba, I. Konishi, M. Mandai. British Journal of Cancer, 2015
671 citations recorded by the source corpus.
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.
Subfields: Immunology, Oncology, Reproductive Medicine
View Paper: https://www.semanticscholar.org/paper/1e2bd736e88dcbd1b1b6038442bc3551c272d9a1
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In Oncology
Citations in the corpus
- Regulatory mechanisms of PD-1/PD-L1 in cancers (2024, background): “IFN-γ, secreted by inflammatory cells such as macrophages and NK cells, upregulates PD-L1 expression on tumor cells [114].”
- The interaction between ferroptosis and lipid metabolism in cancer (2020, background): “For example, IFNγ secreted by activated CD8 T cells upregulates PD-L1 on cancer cells and promotes tumor growth.(134) Thus, combining checkpoint blockade with ferroptosis induced by T cells is a potential therapeutic approach for cancer.”
- PD-1/PD-L1 pathway: current researches in cancer. (2020, background): “It has been demonstrated that IFN-γ causes PD-L1 upregulation in ovarian cancer cells, which is responsible for disease progression, whereas IFN-γ receptor 1 inhibition can reduce PD-L1 expression in acute myeloid leukemia mouse models through the MEK/extracellular signal-regulated kinase (ERK) and ”
- Interferon-Gamma at the Crossroads of Tumor Immune Surveillance or Evasion (2018, background): “One important aspect is the ability of IFN-γ to induce PD-L1 expression in cancer, stromal and myeloid cells to impair effector tumor immunity (181).”