Mild photothermal therapy potentiates anti-PD-L1 treatment for immunologically cold tumors via an all-in-one and all-in-control strategy
Mild photothermal therapy potentiates anti-PD-L1 treatment for immunologically cold tumors via an all-in-one and all-in-control strategy
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温和的光热疗法通过一体化和全控策略增强免疫冷肿瘤的抗 PD-L1 治疗
DOI：
10.1038/s41467-019-12771-9
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发表时间：
2019-10-25
影响因子：
16.6
通讯作者：
Sun, Chunmeng
中科院分区：
文献类型：
--
作者：
Huang, Liping;Li, Yanan;Sun, Chunmeng
免疫检查点阻断抗体的主要挑战之一在于具有有限T细胞应答的恶性肿瘤或免疫学上的“冷”肿瘤。受发热样热诱导免疫有利的肿瘤微环境的能力的启发，提出了温和光热疗法（PTT）以使肿瘤对免疫检查点抑制敏感并使“冷”肿瘤“热”。“在这里，我们提出了一种组合的全合一和全控制策略，以实现局部共生的温和光热辅助免疫疗法（SMPAI）。我们将近红外（NIR）光热剂IR 820和程序性死亡配体1抗体（aPD-L1）装载到具有热可逆凝胶-溶胶相变的有利性质的脂质凝胶储库中。手动控制的近红外辐射调节aPD-L1的释放，更重要的是，增加肿瘤浸润淋巴细胞的募集并增强T细胞对肿瘤的活性。在4 T1和B16 F10模型上的体内抗肿瘤研究表明，SMPAI是治疗“冷”肿瘤的有效且有前途的策略。
One of the main challenges for immune checkpoint blockade antibodies lies in malignancies with limited T-cell responses or immunologically "cold" tumors. Inspired by the capability of fever-like heat in inducing an immune-favorable tumor microenvironment, mild photothermal therapy (PTT) is proposed to sensitize tumors to immune checkpoint inhibition and turn "cold" tumors "hot." Here we present a combined all-in-one and all-in-control strategy to realize a local symbiotic mild photothermal-assisted immunotherapy (SMPAI). We load both a near-infrared (NIR) photothermal agent IR820 and a programmed death-ligand 1 antibody (aPD-L1) into a lipid gel depot with a favorable property of thermally reversible gel-to-sol phase transition. Manually controlled NIR irradiation regulates the release of aPD-L1 and, more importantly, increases the recruitment of tumor-infiltrating lymphocytes and boosts T-cell activity against tumors. In vivo antitumor studies on 4T1 and B16F10 models demonstrate that SMPAI is an effective and promising strategy for treating "cold" tumors.