肿瘤细胞治疗研究
英文原题：Tumor Microenvironment and Immune Response Against Wilms Tumor: Evasion Mechanisms and Implications for Immunotherapeutic Approaches.
Wilms瘤（WT）是儿童期最常见的恶性肾肿瘤，也是儿科肿瘤学的主要成功案例之一，通过风险适应性多模式治疗获得了非常好的生存率。
Wilms瘤（WT）是儿童期最常见的恶性肾肿瘤，也是儿科肿瘤学的主要成功案例之一，通过风险适配的多模式治疗实现了非常好的生存率。然而，一部分患者——特别是那些伴有弥漫性间变、化疗后持续存在的胚芽型肿瘤或复发疾病的患者——仍然面临不良结局和显著的长期治疗相关疾病负担。这些挑战凸显了需要超越传统细胞毒性方法的新型治疗策略。越来越多的证据表明，WT的特征是由其发育起源和三相组织学所塑造的复杂而独特的肿瘤微环境（TME）。免疫细胞浸润、炎症介质和免疫检查点通路与胚芽、上皮和间质肿瘤成分的相互作用各不相同，产生了异质性的免疫监视和免疫逃逸机制。特别是，肿瘤相关巨噬细胞（TAMs）、功能受损的自然杀伤（NK）细胞和免疫抑制性间质成分在塑造可能限制免疫治疗疗效的免疫环境中发挥核心作用。尽管免疫治疗已改变了若干成人恶性肿瘤和部分儿童癌症的管理，但其向WT的转化迄今仍有限，在未选择的患者群体中结果平平。然而，最近的免疫基因组学和蛋白质基因组学研究提示，存在具有不同免疫特征和对靶向免疫治疗方法潜在易感性的生物学上不同的WT亚群。本叙述性综述整合了病理学、免疫学和临床视角，总结了当前关于WT免疫微环境、肿瘤免疫逃逸机制以及新兴免疫治疗策略的知识。通过提供统一框架，旨在支持多学科方法，以合理开发针对特定WT亚组的未来免疫治疗和联合治疗。
Wilms tumor (WT) is the most common malignant renal tumor in childhood and represents one of the major success stories of pediatric oncology, with very good survival achieved through risk-adapted multimodal therapy. Nevertheless, a subset of patients-particularly those with diffuse anaplasia, blastemal-type tumors persisting after chemotherapy, or relapsed disease-continues to experience poor outcomes and significant long-term treatment-related morbidity. These challenges highlight the need for novel therapeutic strategies beyond conventional cytotoxic approaches. Growing evidence indicates that WT is characterized by a complex and distinctive tumor microenvironment (TME) shaped by its developmental origin and triphasic histology. Immune cell infiltration, inflammatory mediators, and immune checkpoint pathways interact differently with blastemal, epithelial, and stromal tumor components, generating heterogeneous immune surveillance and escape mechanisms. In particular, tumor-associated macrophages (TAMs), functionally impaired natural killer (NK) cells, and immunosuppressive stromal elements play a central role in shaping an immune milieu that may limit the efficacy of immune-based therapies. Although immunotherapy has changed the management of several adult malignancies and some pediatric cancers, its translation to WT has so far been limited, with modest results in unselected patient populations. Recent immunogenomic and proteogenomic studies, however, suggest the existence of biologically distinct WT subsets with different immune features and potential susceptibility to targeted immunotherapeutic approaches. This narrative review integrates pathological, immunological, and clinical perspectives to summarize current knowledge on the WT immune microenvironment, mechanisms of tumor immune evasion, and emerging immunotherapeutic strategies. By providing a unified framework, it aims at supporting a multidisciplinary approach for the rational development of future immune-based and combination therapies tailored to specific WT subgroups.
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