Cancer immunotherapy with recombinant poliovirus induces IFN-dominant activation of dendritic cells and tumor antigen-specific CTLs.
Cancer immunotherapy with recombinant poliovirus induces IFN-dominant activation of dendritic cells and tumor antigen-specific CTLs.
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DOI：
10.1126/scitranslmed.aan4220
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发表时间：
2017-09-20
影响因子：
17.1
通讯作者：
Nair SK
中科院分区：
文献类型：
--
作者：
Brown MC;Holl EK;Boczkowski D;Dobrikova E;Mosaheb M;Chandramohan V;Bigner DD;Gromeier M;Nair SK
肿瘤在免疫抑制微环境中茁壮成长，阻碍抗肿瘤的先天性和适应性免疫反应。因此，需要能够克服免疫抑制并参与抗肿瘤免疫的方法。本研究确定了重组脊髓灰质炎：鼻病毒嵌合体PVSRIPO的佐剂和癌症免疫治疗潜力。PVSRIPO目前正在进行针对复发性WHO IV级恶性胶质瘤的临床试验，这是一种众所周知的难治性癌症。肿瘤细胞的致细胞病变感染释放蛋白质组并暴露病原体和损伤相关的分子模式。同时，抗原呈递细胞（如树突状细胞和巨噬细胞）的亚致死性感染在免疫抑制的微环境中产生有效的、持续的I型干扰素显性激活，并促进体外肿瘤抗原特异性T细胞应答和体内抗肿瘤免疫的发展。PVSRIPO的免疫排斥性刺激肿瘤微环境内的典型先天性抗病原体炎症反应，其最终导致树突状细胞和T细胞浸润。我们的研究结果提供了PVSRIPO作为一种有效的肿瘤内免疫佐剂，产生肿瘤抗原特异性CTL应答的机制证据。
Tumors thrive in an immunosuppressive microenvironment that impedes antitumor innate and adaptive immune responses. Thus, approaches that can overcome immunosuppression and engage antitumor immunity are needed. This study defines the adjuvant and cancer immunotherapy potential of the recombinant polio:rhinovirus chimera, PVSRIPO. PVSRIPO is currently in clinical trials against recurrent WHO grade IV malignant glioma, a notoriously treatment-refractory cancer. Cytopathogenic infection of neoplastic cells releases the proteome and exposes pathogen- and damage-associated molecular patterns. At the same time, sublethal infection of antigen-presenting cells, such as dendritic cells and macrophages, yields potent, sustained type I interferon-dominant activation in an immunosuppressed microenvironment and promotes the development of tumor antigen-specific T cell responses in vitro and antitumor immunity in vivo. PVSRIPO’s immune adjuvancy stimulates canonical innate anti-pathogen inflammatory responses within the tumor microenvironment that culminate in dendritic cell and T cell infiltration. Our findings provide mechanistic evidence that PVSRIPO functions as a potent intratumor immune adjuvant that generates tumor antigen-specific CTL responses.
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影响因子：
5.4
作者：
Brown, Michael C.;Dobrikov, Mikhail I.;Gromeier, Matthias
通讯作者：
Gromeier, Matthias
DOI：
10.1084/jem.20101158
发表时间：
2011-09-26
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Diamond MS;Kinder M;Matsushita H;Mashayekhi M;Dunn GP;Archambault JM;Lee H;Arthur CD;White JM;Kalinke U;Murphy KM;Schreiber RD
通讯作者：
Schreiber RD
DOI：
10.1073/pnas.38.8.747
发表时间：
1952-01-01
影响因子：
11.1
作者：
DULBECCO, R
通讯作者：
DULBECCO, R
影响因子：
5.4
作者：
Brown, Michael C.;Bryant, Jeffrey D.;Gromeier, Matthias
通讯作者：
Gromeier, Matthias
DOI：
10.1073/pnas.97.12.6803
发表时间：
2000-06-06
影响因子：
11.1
作者：
Gromeier, M;Lachmann, S;Wimmer, E
通讯作者：
Wimmer, E