肾细胞癌免疫细胞治疗的研究进展

doi:10.3969/j.issn.1674-8115.2025.07.014

摘要/Abstract

摘要：

肾细胞癌（renal cell carcinoma，RCC）是成人最常见的肾脏恶性肿瘤，占所有肾脏肿瘤的90%以上。RCC早期多无明显症状，常在体检或影像学检查中被偶然发现。尽管局限性RCC通过手术切除可获得良好结局，但对于晚期或转移性病例，传统治疗手段如化学治疗、放射治疗及靶向治疗的效果常常有限，预后仍不理想。RCC是一种具有高度免疫原性的肿瘤，能够通过多种机制逃避机体的免疫监视。因此，以细胞治疗为代表的免疫治疗作为一种新兴的治疗方式，近年来备受关注，展现出巨大的潜力。免疫细胞治疗利用患者自身的免疫系统或外源性免疫细胞来增强抗肿瘤免疫反应，恢复免疫系统的功能，从而有效清除肿瘤细胞，已成为治疗RCC的重要研究方向。然而免疫细胞治疗仍面临个体差异、免疫相关不良事件、肿瘤微环境免疫抑制及治疗后耐药等诸多挑战，严重制约其临床疗效提升。该文概括了RCC的免疫逃逸机制，归纳了RCC免疫细胞治疗的进展，分析了RCC免疫细胞治疗的前景，以期为更好地解决难治性RCC提供临床思路和方向。

关键词: 肾细胞癌, 细胞治疗, 免疫治疗, 耐药

Abstract:

Renal cell carcinoma (RCC) is the most common type of malignant kidney tumor in adults, accounting for more than 90% of all renal malignancies. In its early stages, RCC is often asymptomatic and is frequently discovered incidentally during physical examinations or diagnostic imaging. While localized RCC can often be effectively treated with surgical resection, the prognosis for advanced or metastatic cases remains poor, as conventional therapies such as chemotherapy, radiotherapy, and targeted therapy often show suboptimal responses. As a highly immunogenic tumor, RCC is capable of evading immune surveillance through various mechanisms. Therefore, immune therapies, especially cell-based therapies at the forefront, have gained significant attention in recent years as emerging treatment modalities, showing great potential. Immune cell therapy enhances anti-tumor immune responses by utilizing the patient's immune system or exogenous immune cells to restore immune function, thereby effectively eliminating tumor cells. It has become an important research direction for RCC treatment. However, despite its promising clinical prospects, immune cell therapy still faces numerous challenges. Issues such as individual heterogeneity, immune-related adverse events, immune suppression in the tumor microenvironment, and post-treatment drug resistance continue to affect its clinical efficacy. This review summarizes the immune escape mechanisms in RCC, outlines the progress of RCC immune cell therapy, and analyzes its future prospects, aiming to provide insights and direction for better addressing the clinical challenges of refractory RCC.

Key words: renal cell carcinoma, cell therapy, immunotherapy, drug resistance

中图分类号:

R737.11

陈子旋, 刘敏. 肾细胞癌免疫细胞治疗的研究进展[J]. 上海交通大学学报（医学版）, 2025, 45(7): 916-925.

CHEN Zixuan, LIU Min. Research progress on immune cell therapy in renal cell carcinoma[J]. Journal of Shanghai Jiao Tong University (Medical Science), 2025, 45(7): 916-925.

图/表 1

图1 RCC免疫逃逸机制Note： PD-1—programmed death-1; CTLA-4—cytotoxic T-lymphocyte-associated protein 4; TIM-3—T cell immunoglobulin and mucin-domain containing-3; TIGTI—T cell immunoreceptor with Ig and ITIM domain; BTLA—B and T lymphocyte attenuator; VISTA—V-domain Ig suppressor of T cell activation; LAG-3—lymphocyte activation gene 3; HLAⅠ—human leukocyte antigen Ⅰ; TAP1/2—transporter associated with antigen processing 1/2; LMP2—low molecular weight protein 2; VEGF—vascular endothelial growth factor; TGF-β—transforming growth factor β; IL-10—interleukin-10; MMP9—matrix metalloproteinase 9; TNF-α—tumor necrosis factor-α; FOXP3—forkhead box protein P3; 2-HG—2-hydroxyglutarate; PGE2—prostaglandin E2; SA—succinic acid; Bcl-2/XL—B-cell lymphoma-2/B-cell lmyphoma-extra large; IFN-γ—interferon-γ; NF-κB—nuclear factor-κB; NK cell—natural killer cell; DC—dendritic cell; Treg—regulatory T cell; MDSC—myeloid-derived suppressor cell; TAM—tumor-associated macrophage; RCC—renal cell carcinoma.

Fig 1 Mechanisms of immune evasion in RCC

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