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Translational Therapeutics

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”

Abstract

In the article titled “IFN-γ from lymphocytes induces PD-L1 expression and promotes progression of ovarian cancer” in 2015, we showed that PD-L1 expression is induced by IFN-γ 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.

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Fig. 1: Unidirectional interaction of ovarian cancer cells and CTLs.
Fig. 2: Bidirectional interaction of ovarian cancer cells and CTLs.
Fig. 3: Multi-directional interaction of ovarian cancer microenvironment.

Data availability

Data sharing not applicable to this article as no datasets were generated or analysed during the current study.

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We would like to thank Editage (www.editage.com) for English language editing.

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KA drafted the manuscript. JH, NM and MM revised the manuscript. MM supervised the study.

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Correspondence to Kaoru Abiko.

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JH received grants from Ono Pharmaceutical, Sumitomo Dainippon Pharma, KinoPharma and MSD outside the submitted work. NM is an outside director of Takara Bio Inc. NM received a grant and lecture fees from AstraZeneca and received lecture fees from Takeda Pharmaceutical outside the submitted work. The remaining authors declare no competing interests.

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Abiko, K., Hamanishi, J., Matsumura, N. et al. 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”. Br J Cancer (2022). https://doi.org/10.1038/s41416-022-01960-x

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