Patient-derived organoids potentiate precision medicine in advanced clear cell renal cell carcinoma.

IF 5.1 4区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL Precision Clinical Medicine Pub Date : 2022-12-01 DOI:10.1093/pcmedi/pbac028
Yizheng Xue, Bingran Wang, Yiying Tao, Jun Xia, Kedi Yuan, Junhua Zheng, Wei Zhai, Wei Xue
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引用次数: 3

Abstract

To investigate the role of patient-derived organoid (PDO) model in the precision medicine of advanced clear cell renal cell carcinoma (ccRCC), we retrospectively analyzed the clinical data of seven cases of ccRCC diagnosed by operation and pathology in Renji Hospital from September 2021 to September 2022. The seven patients were diagnosed with advanced ccRCC with or without remote metastasis. Cytoreductive and radical nephrectomy was performed respectively. To predict the response to immunotherapy and provide personalized medicine recommendation, a PDO model based on air-liquid interface system was established from the surgical resected tumor and subsequent drug screening was performed. Hematoxylin and eosin (H&E) staining and immunohistochemistry revealed that the PDO recapitulated the histological feature of parent tumor. Immunofluorescence staining identified that CD3+ T cells, SMA+ cancer associated fibroblasts, and CD31+ endothelial cells were preserved in PDO models. Fluorescence activated cell sorter (FACS) revealed an evidently increased ratio of CD8+/CD4+ T cells and apoptotic tumor cells in PDO treated with toripalimab than those treated with IgG4. The results showed that toripalimab is able to rescue the excessive death of CD8+ T cells by critically reversing the immune exhaustion state of ccRCC in PDO model. This research validated that PDO is a promising and faithful preclinical model for prediction of immunotherapy response in patients with ccRCC.

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患者来源的类器官增强了晚期透明细胞肾细胞癌的精准治疗。
为探讨患者源性类器官(PDO)模型在晚期透明细胞肾细胞癌(ccRCC)精准医学中的作用,我们回顾性分析仁集医院2021年9月至2022年9月经手术病理诊断的7例ccRCC的临床资料。7例患者被诊断为晚期ccRCC,伴有或不伴有远处转移。分别行细胞减缩和根治性肾切除术。为了预测对免疫治疗的反应,提供个性化的药物推荐,我们从手术切除的肿瘤中建立了基于气液界面系统的PDO模型,并进行了后续的药物筛选。苏木精和伊红(H&E)染色和免疫组化显示PDO重现了母肿瘤的组织学特征。免疫荧光染色发现,PDO模型中保留了CD3+ T细胞、SMA+癌相关成纤维细胞和CD31+内皮细胞。荧光活化细胞分选(FACS)结果显示,与IgG4组相比,托利莫单抗组PDO中CD8+/CD4+ T细胞和凋亡肿瘤细胞比例明显升高。结果表明,托利哌单抗能够通过严重逆转PDO模型ccRCC的免疫衰竭状态来挽救CD8+ T细胞的过度死亡。本研究验证了PDO是预测ccRCC患者免疫治疗反应的一个有希望和可靠的临床前模型。
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来源期刊
Precision Clinical Medicine
Precision Clinical Medicine MEDICINE, RESEARCH & EXPERIMENTAL-
CiteScore
10.80
自引率
0.00%
发文量
26
审稿时长
5 weeks
期刊介绍: Precision Clinical Medicine (PCM) is an international, peer-reviewed, open access journal that provides timely publication of original research articles, case reports, reviews, editorials, and perspectives across the spectrum of precision medicine. The journal's mission is to deliver new theories, methods, and evidence that enhance disease diagnosis, treatment, prevention, and prognosis, thereby establishing a vital communication platform for clinicians and researchers that has the potential to transform medical practice. PCM encompasses all facets of precision medicine, which involves personalized approaches to diagnosis, treatment, and prevention, tailored to individual patients or patient subgroups based on their unique genetic, phenotypic, or psychosocial profiles. The clinical conditions addressed by the journal include a wide range of areas such as cancer, infectious diseases, inherited diseases, complex diseases, and rare diseases.
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