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免疫生物标志物:它们在人类癌症预后中的表现如何?

Immune biomarkers: how well do they serve prognosis in human cancers?

机构信息

Cancer Immunology and Immunotherapy Center, Saint Savas Cancer Hospital, 171 Alexandras avenue, Athens 11522, Greece.

出版信息

Expert Rev Mol Diagn. 2015 Jan;15(1):49-59. doi: 10.1586/14737159.2015.965684. Epub 2014 Oct 27.

Abstract

In order to be optimally efficacious, therapeutic cancer vaccines must induce robust tumor-specific CD8(+) cytotoxic T cells, which are responsible for tumor cell lysis. Unlike cytotoxic drugs, which act directly on the tumor, cancer vaccines demonstrate new kinetics involving the generation of specific cellular immune responses, which need to be translated into antitumor responses to delay tumor progression and improve survival. These delayed kinetics of action establish a new concept of benefit in the long term, which implies a slow down in tumor growth rates, than a marked reduction in tumor size. Therefore, there is a significant need to identify intermediate biomarkers so that clinical responses can be evaluated in a timely manner. Therapeutic vaccination as a modality for cancer treatment has received significant attention with multiple clinical trials demonstrating improvements in overall survival. Significant challenges to this modality remain, including increasing vaccine potency and minimizing treatment-related toxicities and identifying prognostic and predictive biomarkers of clinical benefit that may guide to select and optimize the therapeutic strategies for patients most likely to gain benefit.

摘要

为了达到最佳疗效,治疗性癌症疫苗必须诱导出强大的肿瘤特异性 CD8(+)细胞毒性 T 细胞,这些细胞负责肿瘤细胞的裂解。与直接作用于肿瘤的细胞毒性药物不同,癌症疫苗表现出涉及特异性细胞免疫反应产生的新的动力学,这些反应需要转化为抗肿瘤反应,以延缓肿瘤进展并提高生存率。这些作用的延迟动力学确立了长期受益的新概念,这意味着肿瘤生长速度的减缓,而不是肿瘤大小的明显减小。因此,有必要确定中间生物标志物,以便及时评估临床反应。治疗性疫苗作为癌症治疗的一种方式已经引起了广泛关注,多项临床试验表明总生存率有所提高。然而,这种方式仍然存在重大挑战,包括提高疫苗效力、最大限度地减少治疗相关毒性以及确定临床获益的预后和预测生物标志物,这些标志物可能有助于选择和优化最有可能受益的患者的治疗策略。

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