Dynamic host immunity and PD-L1/PD-1 blockade efficacy: developments after IFN-γ from lymphocytes induces PD-L1 expression and promotes progression of ovarian cancer

In the article titled IFN-gamma from lymphocytes induces PD-L1 expression and promotes progression of ovarian cancer in 2015, we showed that PD-L1 expression is induced by IFN-gamma from lymphocytes in the tumour microenvironment. This article proposed that PD-L1 expression in cancer cells is not stable but varies among cases, or even within a case, which is influenced by the stromal infiltration of cytotoxic lymphocytes. Immune-checkpoint inhibitors, especially anti-PD-1/PD-L1 therapies, are now widely used to treat various types of cancer. Predictive biomarkers for the efficacy of immune-checkpoint inhibitors include PD-L1 expression, MSI/mismatch repair deficiency and high tumour mutation burden. However, clinical trials have proven that their use in ovarian cancer is still challenging. Reliable biomarkers and new treatment strategies may be sought by elucidating the complex immune microenvironment of ovarian cancer. Although the interaction between cytotoxic lymphocytes and PD-1/PD-L1 on tumour cells is at the centre of therapeutic targets, other immune checkpoints and various immunosuppressive cells also play important roles in ovarian cancer. Targeting these role players in combination with PD-1/PD-L1 blockade may be a promising therapeutic strategy.

Automated summary

In this article, we demonstrated that PD-L1 expression in ovarian cancer is induced by IFN-gamma from lymphocytes in the tumor microenvironment. PD-L1 expression was found to be unstable and influenced by stromal infiltration of cytotoxic lymphocytes. This study highlights the importance of understanding the complex immune microenvironment of ovarian cancer to identify reliable biomarkers and develop new treatment strategies.