ICAM-1 orchestrates the abscopal effect of tumor radiotherapy
ICAM-1 orchestrates the abscopal effect of tumor radiotherapy
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ICAM-1协调肿瘤放射治疗的远隔效应
DOI：
10.1073/pnas.2010333118
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发表时间：
2021-03
期刊：
影响因子：
--
通讯作者：
Zhaofei Liu
中科院分区：
文献类型：
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作者：
Yang Zhao;Ting Zhang;Yanpu Wang;Dehua Lu;Jinhong Du;Xun Feng;Haoyi Zhou;Ning Liu;Hua Zhu;Shangbin Qin;Chenxin Liu;Xianshu Gao;Zhi Yang;Zhaofei Liu
虽然RT作为超过50%的恶性肿瘤患者的一线治疗，但其疗效仅限于局部肿瘤。利用RT的远位效应的努力可以系统地消除扩散到辐射野以外的转移性病变;然而，由于对潜在机制的理解不足以及缺乏可靠的生物标志物进行早期预测，迄今为止，成功有限。在这里，我们证明，非侵入性PET成像的ICAM-1表达赋予预测价值的远端效应的疗效在早期阶段。该策略还可以促进当前或新型药物的潜在高通量筛选，以与RT组合使用，以实现消除原发性和转移性病变的所需抗肿瘤治疗结果。令人信服的证据表明，放射治疗（RT）有一个系统的抑制作用，非照射病变（远位效应），除了消融照射肿瘤。然而，这种作用仅在临床实践中的罕见情况下发生，并且RT的远位作用的潜在机制既未完全理解也未在治疗上利用。在这里，我们确定，细胞间粘附分子-1（ICAM-1），免疫球蛋白超家族的诱导型糖蛋白，上调非辐射肿瘤响应RT。ICAM-1表达在临床前动物模型可以无创检测光学成像和正电子发射断层扫描（PET）使用近红外荧光染料和64铜标记的成像探针，我们合成，分别。重要的是，定量PET成像测定的ICAM-1表达水平与未照射肿瘤的生长呈强负线性相关。此外，通过瘤内注射工程重组腺病毒或全身给予Toll样受体7激动剂封装的纳米药物，ICAM-1表达的遗传或药理学上调可诱导动物模型中对局部RT的远位反应显著增加。机制研究表明，ICAM-1表达可以增强CD 8 + T细胞的活化和肿瘤浸润，以改善未照射肿瘤对RT的反应。总之，我们的研究结果表明，ICAM-1表达的无创PET成像可能是预测未照射肿瘤对RT的反应的有力手段，这可能有助于探索新的联合RT策略，以有效消融原发性和播散性病变。
Significance Although RT serves as a frontline therapy for more than 50% of patients with malignancies, its efficacy is limited to localized tumors. Efforts in harnessing the abscopal effect of RT could systemically eliminate metastatic lesions disseminated beyond the radiation field; however, success has been limited thus far, owing to an inadequate understanding of the underlying mechanisms and an absence of reliable biomarkers for early prediction. Here we demonstrate that noninvasive PET imaging of ICAM-1 expression confers predictive value for abscopal effect efficacy at an early stage. This strategy may also facilitate potential high-throughput screening of current or novel drugs to be used in combination with RT to achieve desired antitumor therapeutic outcomes that eliminate both primary and metastatic lesions. Compelling evidence indicates that radiotherapy (RT) has a systemic inhibitory effect on nonirradiated lesions (abscopal effect) in addition to the ablation of irradiated tumors. However, this effect occurs only in rare circumstances in clinical practice, and mechanisms underlying the abscopal effect of RT are neither fully understood nor therapeutically utilized. Here we identified that intercellular adhesion molecule-1 (ICAM-1), an inducible glycoprotein of the immunoglobulin superfamily, is up-regulated in nonirradiated tumors responsive to RT. ICAM-1 expression in preclinical animal models can be noninvasively detected by optical imaging and positron emission tomography (PET) using near-infrared fluorescence dye- and 64Cu-labeled imaging probes that we synthesized, respectively. Importantly, the expression levels of ICAM-1 determined by quantitative PET imaging showed a strong negative linear correlation with the growth of nonirradiated tumors. Moreover, genetic or pharmacologic up-regulation of ICAM-1 expression by either an intratumoral injection of engineered recombinant adenovirus or systemic administration of a Toll-like receptor 7 agonist-capsulated nanodrug could induce markedly increased abscopal responses to local RT in animal models. Mechanistic investigation revealed that ICAM-1 expression can enhance both the activation and tumor infiltration of CD8+ T cells to improve the responses of the nonirradiated tumors to RT. Together, our findings suggest that noninvasive PET imaging of ICAM-1 expression could be a powerful means to predict the responses of nonirradiated tumors to RT, which could facilitate the exploration of new combination RT strategies for effective ablation of primary and disseminated lesions.
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影响因子：
--
作者：
M. Betts;R. Koup
通讯作者：
M. Betts;R. Koup
影响因子：
16.8
作者：
Rodríguez-Ruiz ME;Vanpouille-Box C;Melero I;Formenti SC;Demaria S
通讯作者：
Demaria S
DOI：
10.1158/1078-0432.ccr-12-0984
发表时间：
2012-12-15
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Dewan MZ;Vanpouille-Box C;Kawashima N;DiNapoli S;Babb JS;Formenti SC;Adams S;Demaria S
通讯作者：
Demaria S
影响因子：
11.5
作者：
Martinez-Lostao, Luis;Anel, Alberto;Pardo, Julian
通讯作者：
Pardo, Julian
与免疫检查点阻断剂一起使用的精准放射治疗。
DOI：
10.1158/1078-0432.ccr-16-0037
发表时间：
2018-01-15
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Vanpouille-Box C;Formenti SC;Demaria S
通讯作者：
Demaria S