Type I interferon signaling in malignant blasts contributes to treatment efficacy in AML patients.
Type I interferon signaling in malignant blasts contributes to treatment efficacy in AML patients.
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DOI：
10.1038/s41419-023-05728-w
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发表时间：
2023-03-24
影响因子：
9
通讯作者：
Fucikova J
中科院分区：
文献类型：
--
作者：
Holicek P;Truxova I;Rakova J;Salek C;Hensler M;Kovar M;Reinis M;Mikyskova R;Pasulka J;Vosahlikova S;Remesova H;Valentova I;Lysak D;Holubova M;Kaspar P;Prochazka J;Kasikova L;Spisek R;Galluzzi L;Fucikova J
虽然I型干扰素因其抗病毒感染的关键作用而广为人知，但越来越多的临床前和临床数据表明，在肿瘤微环境中产生强大的I型干扰素可促进癌症免疫监视，并有助于各种抗肿瘤药物的疗效，特别是免疫原性细胞死亡诱导剂。在这里，我们报告了急性髓系白血病(AML)患者的恶性原始细胞通过Toll样受体3(TLR3)依赖的机制释放I型干扰素，该机制不受治疗的驱动。在这些患者中，I型干扰素刺激抗癌免疫反应的能力被恶性细胞诱导的免疫抑制机制所消除，而I型干扰素在原代AML原始细胞、AML患者的白血病干细胞和AML异种移植模型中具有直接的细胞抑制、细胞毒和化疗增敏活性。最后，在132名AML患者的队列中，发现I型干扰素信号的遗传特征对无复发生存期和总生存期具有独立的预后价值。这些发现描绘了一种临床上相关的、可操作的治疗和预测信息的机制，通过该机制，I型干扰素在急性髓细胞白血病患者中介导了有益的效果。
While type I interferon (IFN) is best known for its key role against viral infection, accumulating preclinical and clinical data indicate that robust type I IFN production in the tumor microenvironment promotes cancer immunosurveillance and contributes to the efficacy of various antineoplastic agents, notably immunogenic cell death inducers. Here, we report that malignant blasts from patients with acute myeloid leukemia (AML) release type I IFN via a Toll-like receptor 3 (TLR3)-dependent mechanism that is not driven by treatment. While in these patients the ability of type I IFN to stimulate anticancer immune responses was abolished by immunosuppressive mechanisms elicited by malignant blasts, type I IFN turned out to exert direct cytostatic, cytotoxic and chemosensitizing activity in primary AML blasts, leukemic stem cells from AML patients and AML xenograft models. Finally, a genetic signature of type I IFN signaling was found to have independent prognostic value on relapse-free survival and overall survival in a cohort of 132 AML patients. These findings delineate a clinically relevant, therapeutically actionable and prognostically informative mechanism through which type I IFN mediates beneficial effects in patients with AML.
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影响因子：
30.5
作者：
Musella, Martina;Guarracino, Andrea;Manduca, Nicoletta;Galassi, Claudia;Ruggiero, Eliana;Potenza, Alessia;Maccafeo, Ester;Manic, Gwenola;Mattiello, Luca;Rehim, Sara Soliman Abdel;Signore, Michele;Pietrosanto, Marco;Helmer-Citterich, Manuela;Pallocca, Matteo;Fanciulli, Maurizio;Bruno, Tiziana;De Nicola, Francesca;Corleone, Giacomo;Di Benedetto, Anna;Ercolani, Cristiana;Pescarmona, Edoardo;Pizzuti, Laura;Guidi, Francesco;Sperati, Francesca;Vitale, Sara;Macchia, Daniele;Spada, Massimo;Schiavoni, Giovanna;Mattei, Fabrizio;De Ninno, Adele;Businaro, Luca;Lucarini, Valeria;Bracci, Laura;Arico, Eleonora;Ziccheddu, Giovanna;Facchiano, Francesco;Rossi, Stefania;Sanchez, Massimo;Boe, Alessandra;Biffoni, Mauro;De Maria, Ruggero;Vitale, Ilio;Sistigu, Antonella
通讯作者：
Sistigu, Antonella
影响因子：
3.7
作者：
Linsley PS;Speake C;Whalen E;Chaussabel D
通讯作者：
Chaussabel D
影响因子：
2.6
作者：
Jiang, Hao;Liu, Xiao-Hong;Huang, Xiao-Jun
通讯作者：
Huang, Xiao-Jun
影响因子：
7.8
作者：
Lukhele S;Boukhaled GM;Brooks DG
通讯作者：
Brooks DG
1型干扰素可以防止同种异体移植后白血病复发。
影响因子：
7.5
作者：
Magenau, John M.;Peltier, Dan;Riwes, Mary;Pawarode, Attaphol;Parkin, Brian;Braun, Thomas;Anand, Sarah;Ghosh, Monalisa;Maciejewski, John;Yanik, Gregory;Choi, Sung Won;Talpaz, Moshe;Reddy, Pavan
通讯作者：
Reddy, Pavan