<br>IRF1 转录因子在抗肿瘤免疫中的肿瘤-细胞-内在和-外在作用相反,Cell Reports

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IRF1 转录因子在抗肿瘤免疫中的肿瘤-细胞-内在和-外在作用相反
Cell Reports ( IF 7.5 ) Pub Date : 2024-06-02 , DOI: 10.1016/j.celrep.2024.114289
Prabhat K Purbey ₁ , Joowon Seo ₂ , Manash K Paul ₃ , Keisuke S Iwamoto ₄ , Allison E Daly ₅ , An-Chieh Feng ₅ , Ameya S Champhekar ₆ , Justin Langerman ₇ , Katie M Campbell ₆ , Dörthe Schaue ₄ , William H McBride ₄ , Steven M Dubinett ₈ , Antoni Ribas ₉ , Stephen T Smale ₁₀ , Philip O Scumpia ₁₁

Affiliation

Department of Medicine, Division of Dermatology, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA; Department of Microbiology, Immunology, and Molecular Genetics, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA.
Department of Medicine, Division of Dermatology, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA.
Department of Medicine, Division of Pulmonology and Critical Care Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA; Department of Radiation Biology and Toxicology, Manipal School of Life Sciences, Manipal Academy of Higher Education, Manipal, Karnataka 576104, India.
Department of Radiation Oncology, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA.
Department of Microbiology, Immunology, and Molecular Genetics, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA.
Department of Medicine, Division of Hematology-Oncology, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA.
Department of Biological Chemistry, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA.
Department of Medicine, Division of Pulmonology and Critical Care Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA; Jonsson Comprehensive Cancer Center, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA; Howard Hughes Medical Institute, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA.
Department of Medicine, Division of Hematology-Oncology, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA; Jonsson Comprehensive Cancer Center, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA.
Department of Microbiology, Immunology, and Molecular Genetics, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA; Jonsson Comprehensive Cancer Center, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA; Howard Hughes Medical Institute, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA.
Department of Medicine, Division of Dermatology, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA; Jonsson Comprehensive Cancer Center, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA; VA Greater Los Angeles Healthcare System, Los Angeles, CA 90073, USA.

I 型干扰素（IFN-I）和 IFN-γ 通过促进 T 细胞反应来增强抗肿瘤免疫力。矛盾的是，IFN 可能通过激活免疫检查点来促进 T 细胞耗竭。这些不同反应的下游调节因素尚不完全清楚。在这里，我们描述了干扰素调节因子 1 （IRF1）如何协调 IFN 的这些相反作用。IRF1 在肿瘤细胞中的表达通过阻止免疫细胞中的干扰素刺激基因（ISG）和效应程序来阻断 Toll 样受体和 IFN-I 依赖性宿主抗肿瘤免疫。相反，抗肿瘤免疫需要宿主中 IRF1 的表达。从机制上讲，IRF1 在肿瘤细胞中免疫抑制性而非免疫刺激性 ISG 的启动子处明显结合或与 STAT1 结合。肿瘤中程序性细胞死亡配体 1 （PD-L1）的过表达仅部分恢复肿瘤生长，表明 IRF1 对抗肿瘤免疫的多因素影响。因此，我们发现肿瘤细胞中的 IRF1 表达对抗宿主 IFN-I 和 IRF1 依赖性抗肿瘤免疫，以促进免疫逃逸和肿瘤生长。

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更新日期：2024-06-02

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