Intrapleural nano-immunotherapy promotes innate and adaptive immune responses to enhance anti-PD-L1 therapy for malignant pleural effusion.
Intrapleural nano-immunotherapy promotes innate and adaptive immune responses to enhance anti-PD-L1 therapy for malignant pleural effusion.
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DOI：
10.1038/s41565-021-01032-w
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发表时间：
2022-03
影响因子：
38.3
通讯作者：
中科院分区：
文献类型：
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作者：
恶性胸腔积液（MPE）是晚期恶性肿瘤的指征，具有一致的致命预后。通常，肿瘤微环境的两个不同区室，积液和播散性胸膜肿瘤，在胸膜腔中共存，这对治疗干预和药物递送提出了重大挑战。临床证据表明，MPE包含大量具有肿瘤促进表型的肿瘤相关骨髓细胞，从而损害抗肿瘤免疫。在这里，我们开发了一种装载有环状二核苷酸（LNP-CDN）的脂质体纳米颗粒，用于靶向激活巨噬细胞和树突状细胞中干扰素基因信号传导的刺激物，并表明在胸膜内给药时，它们诱导MPE中转录景观的急剧变化，减轻积液和胸膜肿瘤中的免疫冷MPE。此外，联合免疫治疗与程序性死亡配体1的阻断有效地减少MPE体积，并抑制肿瘤生长，不仅在胸膜腔，而且在肺实质中，赋予显着延长的生存MPE荷瘤小鼠。此外，LNP-CDN诱导的免疫效应也在临床MPE样品中观察到，表明胸膜内LNP-CDN用于临床MPE免疫治疗的潜力。
Malignant pleural effusion (MPE) is indicative of terminal malignancy with a uniformly fatal prognosis. Often, two distinct compartments of tumour microenvironment, the effusion and disseminated pleural tumours, co-exist in the pleural cavity, presenting a major challenge for therapeutic interventions and drug delivery. Clinical evidence suggests that MPE comprises abundant tumour-associated myeloid cells with the tumour-promoting phenotype, impairing antitumour immunity. Here we developed a liposomal nanoparticle loaded with cyclic dinucleotide (LNP-CDN) for targeted activation of stimulators of interferon genes signalling in macrophages and dendritic cells and showed that, on intrapleural administration, they induce drastic changes in the transcriptional landscape in MPE, mitigating the immune cold MPE in both effusion and pleural tumours. Moreover, combination immunotherapy with blockade of programmed death ligand 1 potently reduced MPE volume and inhibited tumour growth not only in the pleural cavity but also in the lung parenchyma, conferring significantly prolonged survival of MPE-bearing mice. Furthermore, the LNP-CDN-induced immunological effects were also observed with clinical MPE samples, suggesting the potential of intrapleural LNP-CDN for clinical MPE immunotherapy.
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DOI：
10.1084/jem.20101159
发表时间：
2011-09-26
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Fuertes MB;Kacha AK;Kline J;Woo SR;Kranz DM;Murphy KM;Gajewski TF
通讯作者：
Gajewski TF
影响因子：
82.9
作者：
Gattinoni L;Speiser DE;Lichterfeld M;Bonini C
通讯作者：
Bonini C
DOI：
10.1038/nri3921
发表时间：
2015-12
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
通讯作者：
--
影响因子：
4.1
作者：
Bosi A;Zanellato S;Bassani B;Albini A;Musco A;Cattoni M;Desio M;Nardecchia E;D'Urso DG;Imperatori A;Dominioni L;Noonan DM;Mortara L;Bruno A
通讯作者：
Bruno A
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