南方医科大学学报

南方医科大学学报 ›› 2025, Vol. 45 ›› Issue (6): 1280-1288.doi: 10.12122/j.issn.1673-4254.2025.06.17

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肾透明细胞癌患者的免疫细胞浸润特征与临床病理参数具有相关性

赵华轩1(), 张桂潮1, 刘家荣3, 莫富添3, 李韬恩3, 类成勇3(), 吕世栋2()   

  1. 1.南方医科大学口腔医学院，广东 广州 510515
    2.广东省人民医院泌尿外科，广东 广州 510080
    3.南方医科大学南方医院泌尿外科，广东 广州 510515
  • 收稿日期:2025-04-06 出版日期:2025-06-20 发布日期:2025-06-27
  • 通讯作者: 类成勇,吕世栋 E-mail:2974463417@qq.com;345041047@qq.com;lsd990@smu.edu.cn
  • 作者简介:赵华轩，在读本科生，E-mail: 2974463417@qq.com
  • 基金资助:
    广东省自然科学基金(2024A1515010331);南方医科大学南方医院院长基金(2019B006)

Correlations of immune cell infiltration characteristics with clinicopathological parameters in patients with clear cell renal cell carcinoma

Huaxuan ZHAO1(), Guichao ZHANG1, Jiarong LIU3, Futian MO3, Taoen LI3, Chengyong LEI3(), Shidong LÜ2()   

  1. 1.School of Stomatology, Southern Medical University, Guangzhou 510515, China
    2.Department of Urology, Guangdong Provincial People's Hospital, Guangzhou 510080, China
    3.Department of Urology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China
  • Received:2025-04-06 Online:2025-06-20 Published:2025-06-27
  • Contact: Chengyong LEI, Shidong Lü E-mail:2974463417@qq.com;345041047@qq.com;lsd990@smu.edu.cn

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摘要：

目的 考察中国人群肾透明细胞癌患者肿瘤样本中免疫细胞浸润特征，并分析免疫细胞浸润与疾病分期及免疫治疗应答的相关性。 方法 收集南方医科大学南方医院2020年10月~2023年10月154例肾透明细胞癌患者的肿瘤样本和临床病理信息，通过免疫组织化学、免疫荧光等方法鉴定肿瘤组织中浸润免疫细胞类型，并同患者临床病理特征进行相关性分析。对其中22例患者的肿瘤组织构建了患者来源的肿瘤组织片段（PDTF）模型，利用PD-1单抗处理，后使用流式细胞术检测了T细胞活化情况，评估患者免疫治疗应答。 结果 我国肾透明细胞癌患者中，CD8+ T细胞、CD4+ T细胞和CD3+ T细胞浸润最丰富。病例相关分析表明，CD3+ T细胞（P=0.004）、PD-1+ T细胞（P=0.020）、CD68+ T细胞（P=0.049）、CD79+ T细胞（P=0.049）以及Tryptase+细胞（P=0.049）的浸润与更大的肿瘤体积（≥5 cm）呈正相关；CD4+ T细胞浸润程与肿瘤分期成负相关（P=0.026）。高ISUP分级患者CD3+ T细胞（P=0.023）、CD8+ T细胞（P=0.045）、PD-1+ T细胞（P=0.014）、CD20+ B细胞（P=0.020）、CD79+ B细胞（P=0.004）浸润浸润水平较高，但具有较低的Traptase+细胞浸润（P=0.001）。具有丰富免疫细胞浸润的患者也倾向更好的免疫治疗应答。 结论 本研究揭示了中国人群肾透明细胞癌患者免疫细胞浸润特征，发现不同患者免疫细胞浸润存在显著异质性，证实免疫细胞浸润程度与临床病理参数存在密切关联。

关键词: 肾透明细胞癌, 肿瘤免疫细胞浸润, 患者来源的肿瘤组织片段模型

Abstract:

Objective To investigate the characteristics of immune cell infiltration in tumor samples from Chinese patients with clear cell renal cell carcinoma (ccRCC) and the correlation of immune cell infiltration with tumor stage and response to immunotherapy. Methods Tumor samples and clinicopathological data were collected from 154 ccRCC patients treated in Nanfang Hospital, Southern Medical University from October, 2020 to October, 2023. The immune cell types infiltrating the tumor tissues were identified using immunohistochemistry and immunofluorescence staining, and their correlations with the patients' clinicopathological characteristics were analyzed. Patient-derived tumor tissue fragment models (PDTF) models, constructed using tumor tissues from 22 patients, were treated with PD-1 monoclonal antibody, and T cell activation was detected using flow cytometry to assess the patients' responses to immunotherapy. Results In Chinese ccRCC patients included in this study, CD8+ T cells, CD4+ T cells, and CD3+ T cells were the most abundant in the tumor tissues. Higher infiltration levels of CD3+ T cells (P=0.004), PD-1+ T cells (P=0.020), CD68+ T cells (P=0.049), CD79+ T cells (P=0.049), and Tryptase+ cells (P=0.049) were all positively correlated with a larger tumor size (≥5 cm). A higher infiltration level of CD4+ T cells was associated with a lower tumor stage. Patients with higher International Society of Urological Pathology (ISUP) grades had higher infiltration levels of CD3+ T cells (P=0.023), CD8+ T cells (P=0.045), PD-1+ T cells (P=0.014), CD20+ B cells (P=0.020) and CD79+ B cells (P=0.049), and lower levels of Tryptase+ cells (P=0.001). Patients with abundant infiltrating immune cells tended to have better responses to immunotherapy. Conclusion The infiltrating immune cells are heterogeneous in Chinese ccRCC patients, and immune cell infiltration characteristics are closely correlated with clinicopathological parameters of the patients.

Key words: clear cell renal cell carcinoma, tumor-infiltrating lymphocytes, patient-derived tumor tissue fragment models