靶向巨噬细胞的癌症治疗策略
Macrophage-directed therapeutic strategies in cancer.
肿瘤相关巨噬细胞(TAMs)是肿瘤微环境的主要组成部分,具有显著的功能可塑性,根据所处的微环境信号,既可表现为促进肿瘤进展的免疫抑制细胞,也可表现为支持抗肿瘤免疫的免疫刺激细胞。
英文原题:Emerging Immunotherapy Approaches for Advanced Clear Cell Renal Cell Carcinoma.
肾细胞癌最常见的亚型是透明细胞肾细胞癌(ccRCC)。
肾细胞癌最常见的亚型是透明细胞肾细胞癌(ccRCC)。虽然局限性ccRCC可以通过手术治愈,但转移性疾病预后较差。近年来,免疫治疗已成为晚期ccRCC的一种有前景的治疗方法。本综述全面概述了转移性ccRCC不断演变的免疫治疗格局。免疫检查点抑制剂(ICIs)如PD-1/PD-L1和CTLA-4抑制剂已证明作为单药治疗和联合方案的临床疗效。将ICIs与抗血管生成药物、其他免疫调节剂或新型治疗平台(如双特异性抗体和嵌合抗原受体(CAR)T细胞疗法)配对的联合免疫治疗是活跃的研究领域。除检查点阻断外,包括治疗性疫苗、细胞因子和溶瘤病毒在内的其他模式也正在针对ccRCC进行探索。本综述讨论了这些新兴免疫治疗的机制、主要临床试验、挑战和未来方向。虽然当前策略在改善患者预后方面已显示出前景,但持续研究对于扩展和优化晚期ccRCC的免疫治疗方法至关重要。实现免疫治疗的全部潜力需要阐明应答和耐药的机制、开发预测性生物标志物,以及合理设计针对个体患者定制的联合治疗方案。免疫治疗的进展在改变转移性ccRCC的管理方面具有巨大前景。
The most common subtype of renal cell carcinoma is clear cell renal cell carcinoma (ccRCC). While localized ccRCC can be cured with surgery, metastatic disease has a poor prognosis. Recently, immunotherapy has emerged as a promising approach for advanced ccRCC. This review provides a comprehensive overview of the evolving immunotherapeutic landscape for metastatic ccRCC. Immune checkpoint inhibitors (ICIs) like PD-1/PD-L1 and CTLA-4 inhibitors have demonstrated clinical efficacy as monotherapies and in combination regimens. Combination immunotherapies pairing ICIs with antiangiogenic agents, other immunomodulators, or novel therapeutic platforms such as bispecific antibodies and chimeric antigen receptor (CAR) T-cell therapy are areas of active research. Beyond the checkpoint blockade, additional modalities including therapeutic vaccines, cytokines, and oncolytic viruses are also being explored for ccRCC. This review discusses the mechanisms, major clinical trials, challenges, and future directions for these emerging immunotherapies. While current strategies have shown promise in improving patient outcomes, continued research is critical for expanding and optimizing immunotherapy approaches for advanced ccRCC. Realizing the full potential of immunotherapy will require elucidating mechanisms of response and resistance, developing predictive biomarkers, and rationally designing combination therapeutic regimens tailored to individual patients. Advances in immunotherapy carry immense promise for transforming the management of metastatic ccRCC.
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