J Transl Med. 2013 Mar 3;11:54. doi: 10.1186/1479-5876-11-54.
Recent investigations of the tumor microenvironment have shown that many tumors are infiltrated by inflammatory and lymphocytic cells. Increasing evidence suggests that the number, type and location of these tumor-infiltrating lymphocytes in primary tumors has prognostic value, and this has led to the development of an 'immunoscore. As well as providing useful prognostic information, the immunoscore concept also has the potential to help predict response to treatment, thereby improving decision- making with regard to choice of therapy. This predictive aspect of the tumor microenvironment forms the basis for the concept of immunoprofiling, which can be described as 'using an individual's immune system signature (or profile) to predict that patient's response to therapy' The immunoprofile of an individual can be genetically determined or tumor-induced (and therefore dynamic). Ipilimumab is the first in a series of immunomodulating antibodies and has been shown to be associated with improved overall survival in patients with advanced melanoma. Other immunotherapies in development include anti-programmed death 1 protein (nivolumab), anti-PD-ligand 1, anti-CD137 (urelumab), and anti-OX40. Biomarkers that can be used as predictive factors for these treatments have not yet been clinically validated. However, there is already evidence that the tumor microenvironment can have a predictive role, with clinical activity of ipilimumab related to high baseline expression of the immune-related genes FoxP3 and indoleamine 2,3-dioxygenase and an increase in tumor-infiltrating lymphocytes. These biomarkers could represent the first potential proposal for an immunoprofiling panel in patients for whom anti-CTLA-4 therapy is being considered, although prospective data are required. In conclusion, the evaluation of systemic and local immunological biomarkers could offer useful prognostic information and facilitate clinical decision making. The challenge will be to identify the individual immunoprofile of each patient and the consequent choice of optimal therapy or combination of therapies to be used.
最近对肿瘤微环境的研究表明，许多肿瘤都被炎症和淋巴细胞浸润。越来越多的证据表明，原发性肿瘤中这些肿瘤浸润淋巴细胞的数量、类型和位置具有预后价值，这导致了“免疫评分”的发展。免疫评分不仅提供了有用的预后信息，还具有预测治疗反应的潜力，从而改善治疗选择的决策。肿瘤微环境的预测方面构成了免疫分析概念的基础，免疫分析可以描述为“利用个体的免疫系统特征（或特征谱）来预测该患者对治疗的反应”。个体的免疫谱可以是遗传决定的，也可以是肿瘤诱导的（因此是动态的）。伊匹单抗是一系列免疫调节抗体中的第一种，已被证明与晚期黑色素瘤患者的总生存改善相关。其他正在开发的免疫疗法包括抗程序性死亡蛋白 1 蛋白（纳武单抗）、抗 PD-配体 1、抗-CD137（urelumab）和抗-OX40。尚未在临床上验证可作为这些治疗预测因素的生物标志物。然而，已经有证据表明肿瘤微环境可以具有预测作用，伊匹单抗的临床活性与免疫相关基因 FoxP3 和吲哚胺 2,3-双加氧酶的基线高表达以及肿瘤浸润淋巴细胞的增加有关。这些生物标志物可能代表了第一个用于正在考虑抗 CTLA-4 治疗的患者的免疫分析面板的潜在建议，尽管需要前瞻性数据。总之，评估系统和局部免疫生物标志物可以提供有用的预后信息并促进临床决策。挑战将是确定每个患者的个体免疫谱以及随之而来的最佳治疗或联合治疗方案的选择。
