Interferon-γ increases sensitivity to chemotherapy and provides immunotherapy targets in models of metastatic castration-resistant prostate cancer.
Interferon-γ increases sensitivity to chemotherapy and provides immunotherapy targets in models of metastatic castration-resistant prostate cancer.
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干扰素-γ增加了对化疗的敏感性，并在转移性去势抵抗性前列腺癌模型中提供了免疫治疗靶标。
DOI：
10.1038/s41598-022-10724-9
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发表时间：
2022-04-22
影响因子：
4.6
通讯作者：
Clark, Amanda M.
中科院分区：
文献类型：
--
作者：
Korentzelos, Dimitrios;Wells, Alan;Clark, Amanda M.
干扰素-γ（IFNγ）是一种细胞因子，迄今为止在癌症临床试验中的获益证据有限。然而，它可能通过诱导抗原呈递途径并同时为免疫检查点阻断治疗提供靶点，在增强免疫学“冷”转移性去势抵抗性前列腺癌（mCRPC）的抗肿瘤免疫力方面发挥作用。此外，基于其对细胞表型的多效性作用，它还可以增加对化疗的敏感性。在这里，我们发现IFNγ处理诱导前列腺癌细胞体外表达主要组织相容性I类（MHC-I）基因和PD-L1。此外，IFNγ治疗导致E-cadherin表达降低，从而增加体外化疗的敏感性。在自发性转移性前列腺癌的体内鼠肿瘤模型中，与对照组和单药治疗组的弥漫性转移性疾病相比，IFNγ全身预处理上调了原发性肿瘤中HLA-A的表达并降低了E-钙粘蛋白的表达，更重要的是，在转移部位，与紫杉醇联合治疗导致细胞凋亡增加和微转移受限。这些结果表明，IFNγ可能有助于联合方案诱导mCRPC肝转移对免疫治疗和化疗的敏感性。
Interferon-γ (IFNγ) is a cytokine with limited evidence of benefit in cancer clinical trials to date. However, it could potentially play a role in potentiating anti-tumor immunity in the immunologically "cold" metastatic castration-resistant prostate cancer (mCRPC) by inducing antigen presentation pathways and concurrently providing targets for immune checkpoint blockade therapy. Moreover, it could additionally increase sensitivity to chemotherapy based on its pleiotropic effects on cell phenotype. Here, we show that IFNγ treatment induced expression of major histocompatibility class-I (MHC-I) genes and PD-L1 in prostate cancer cells in vitro. Furthermore, IFNγ treatment led to a decrease in E-cadherin expression with a consequent increase in sensitivity to chemotherapy in vitro. In an in vivo murine tumor model of spontaneous metastatic prostate cancer, IFNγ systemic pretreatment upregulated the expression of HLA-A and decreased E-cadherin expression in the primary tumor, and more importantly in the metastatic site led to increased apoptosis and limited micrometastases in combination with paclitaxel treatment compared to diffuse metastatic disease in control and monotherapy treatment groups. These findings suggest that IFNγ may be useful in combinatorial regimens to induce sensitivity to immunotherapy and chemotherapy in hepatic metastases of mCRPC.
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影响因子：
64.8
作者：
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影响因子：
10.9
作者：
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通讯作者：
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影响因子：
5.5
作者：
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通讯作者：
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