Figlin Robert A
Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, 8700 Beverly Boulevard, Saperstein Critical Care Tower 1S28, Los Angeles, CA 90048, USA.
Immunotherapy. 2014;6(3):261-8. doi: 10.2217/imt.13.168. Epub 2013 Dec 19.
The historical treatment paradigm for metastatic renal cell carcinoma has focused on immunomodulatory agents, such as IFN-α and IL-2, which provide good clinical outcomes in only a subset of patients. The development of therapies that target the VEGF and mTOR pathways have significantly altered the treatment landscape for this disease, with novel inhibitors providing substantial improvements in progression-free and overall survival over previous standards of care. Despite these advances, toxicity from targeted therapy and the development of resistance results in disease progression. By contrast, vaccine-based immunotherapy represents a promising new approach for the treatment of patients with metastatic renal cell carcinoma; however, tumor-induced immunosuppression has limited the clinical efficacy of this modality until recently. Some evidence suggests that certain targeted therapies, such as sunitinib, may reduce this immunosuppression and enhance the tumor microenvironment to promote synergy with autologous dendritic cell vaccines.
转移性肾细胞癌的传统治疗模式主要集中在免疫调节药物上,如干扰素-α和白细胞介素-2,这些药物仅在部分患者中能带来良好的临床效果。针对血管内皮生长因子(VEGF)和雷帕霉素靶蛋白(mTOR)通路的疗法的发展显著改变了该疾病的治疗格局,新型抑制剂在无进展生存期和总生存期方面比以往的标准治疗有了实质性改善。尽管取得了这些进展,但靶向治疗的毒性和耐药性的出现仍导致疾病进展。相比之下,基于疫苗的免疫疗法是治疗转移性肾细胞癌患者的一种有前景的新方法;然而,直到最近,肿瘤诱导的免疫抑制限制了这种治疗方式的临床疗效。一些证据表明,某些靶向治疗,如舒尼替尼,可能会减少这种免疫抑制并增强肿瘤微环境,以促进与自体树突状细胞疫苗的协同作用。