IFNγ/PD-L1 Signaling Improves the Responsiveness of Anti-PD-1 Therapy in Colorectal Cancer: An in vitro Study

作者：Wenli Yuan, De‐Yao Deng, Hanyu Li, Xinghui Hu, Xueqin Shang, Xia Hou, Hongchao Jiang, Hongchun He · 发表于：OncoTargets and Therapy · 年份：2021 · DOI：10.2147/ott.s294136 · 被引用次数：9 · 研究领域：Cancer Immunotherapy and Biomarkers、Cytokine Signaling Pathways and Interactions、interferon and immune responses

Introduction: Programmed cell death 1 ligand 1 (PD-L1) can be upregulated in cancer cells via interferon gamma (IFNγ) in the tumor microenvironment. IFNγ/PD-L1 signaling is associated with the response to immune checkpoint blockade in melanoma patients. Our previous investigation indicated that the microsatellite instability-high (MSI-H) cell line might exhibit selective hyperresponsiveness to IFNγ treatment, which contributes to increased PD-L1 expression and may be a mechanism of response to anti-PD-1 therapy in colorectal cancer. Methods: The present study evaluated the expression of PD-L1 in a set of MSI and microsatellite stability (MSS) cell lines with IFNγ treatment. The differential signaling molecules associated with signal transducer and activator of transcription (STAT) contributing to hyperresponsiveness to IFNγ exposure were also investigated. Furthermore, we established a coculture assay containing CT26 cells with higher expression of PD-L1 and peripheral blood mononuclear cells (PBMCs) in vitro. Changes in cancer cell viability as well as apoptosis status in response to anti-PD-1 therapy were demonstrated. We further observed changes in the percentage of CD4 + and CD8 + lymphocytes after PD-1 immunotherapy in the coculture assay. Finally, the average extent of inflammation and adaptive immunity factors in the assay was also investigated. Results: This in vitro study revealed that the MSI cell line might exhibit hyperresponsiveness to IFNγ exposure, and IFNγ ind...