肿瘤细胞治疗研究
英文原题：Cancer Immunotherapy with Lipid Nanoparticles Loaded with a Stimulator of Interferon Genes Agonist against Renal Tumor Lung Metastasis.
Cancer Immunotherapy with Lipid Nanoparticles Loaded with a Stimulator of Interferon Genes Agonist against Renal Tumor Lung Metastasis.
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转移性肾细胞癌（RCC）预后较差，主要转移器官是肺。免疫检查点抑制剂（ICIs）免疫治疗是一线治疗，但缓解率较低。因此，开发针对转移性RCC更有效的免疫治疗将非常可取。我们此前已证明，载有干扰素基因刺激因子（STING）激动剂的脂质纳米颗粒（STING-LNPs）如何显著激活自然杀伤（NK）细胞，并对已显示ICI耐药的黑色素瘤肺转移病例诱导抗肿瘤效应。在本研究中，我们评估了使用STING-LNPs治疗肺转移性RCC（Renca）的潜力。静脉注射STING-LNPs可显著减少Renca肿瘤集落数量。相比之下，使用ICIs的单一疗法未显示抗肿瘤效应，甚至ICI与STING-LNP疗法联合也未能增强抗肿瘤效应。主要效应细胞可能是NK细胞，STING-LNPs对NK细胞的激活可能避免免疫检查点分子表达增加。这些发现为开发针对转移性RCC的有效免疫治疗提供了有益见解。
Metastatic renal cell carcinoma (RCC) has a poor prognosis, and the major organ of metastasis is the lung. Immunotherapy with immune checkpoint inhibitors (ICIs) is the first-line therapy, but the response rates are low.
Thus, the development of a more effective immunotherapy against metastatic RCC would be highly desirable.
We previously demonstrated how a stimulator of an interferon gene (STING) agonist-loaded lipid nanoparticles (STING-LNPs) significantly activates natural killer (NK) cells and induces an antitumor effect against cases of melanoma lung metastasis that have shown ICI resistance. In this study, we evaluated the potential of using STING-LNPs in the treatment of lung metastatic RCC (Renca).
An intravenous injection of STING-LNPs drastically decreased the amount of Renca tumor colonies. In contrast, monotherapies using ICIs showed no antitumor effect, and even a combination of ICI and STING-LNP therapies failed to enhance the antitumor effects. The main effector cells would be NK cells, and the activation of NK cells by the STING-LNPs may avoid the increased expression of immune checkpoint molecules.
These findings provide useful insights into the development of an effective immunotherapy against metastatic RCC.
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