Department of Neurosurgery, Karolinska University Hospital Stockholm, Sweden.
Lancet Oncol. 2013 May;14(6):e218-28. doi: 10.1016/S1470-2045(12)70582-X.
Active, but dysfunctional, immune responses in patients with cancer have been studied in several tumour types, but owing to the heterogeneity of cancer theories of common reaction mechanisms seem to be obsolete. In this Review of published clinical studies of patients with cancer, expression and interplay of the following cytokines are examined: interleukin 2, interleukin 6, interleukin 8, interleukin 10, interleukin 12, interleukin 18, tumour necrosis factor α (TNFα), transforming growth factor β (TGFβ), interferon-γ, HLA-DR, macrophage migration inhibitory factor (MIF), and C-X-C motif chemokine receptor 4 (CXCR4). Clinical data were analysed in a non-quantitative descriptive manner and interpreted with regard to experimentally established physiological cytokine interactions. The clinical cytokine pattern that emerged suggests that simultaneous immunostimulation and immunosuppression occur in patients with cancer, with increased concentrations of the cytokines MIF, TNFα, interleukin 6, interleukin 8, interleukin 10, interleukin 18, and TGFβ. This specific cytokine pattern seems to have a prognostic effect, since high interleukin 6 or interleukin 10 serum concentrations are associated with negative prognoses in independent cancer types. Although immunostimulatory cytokines are involved in local cancer-associated inflammation, cancer cells seem to be protected from immunological eradication by cytokine-mediated local immunosuppression and a resulting defect of the interleukin 12-interferon-γ-HLA-DR axis. Cytokines produced by tumours might have a pivotal role in this defect. A working hypothesis is that the cancer-specific and histology-independent uniform cytokine cascade is one of the manifestations of the underlying paraneoplastic systemic disease, and this hypothesis links the stage of cancer with both the functional status of the immune system and the patient's prognosis. Neutralisation of this cytokine pattern could offer novel and so far unexploited treatment approaches for cancer.
在多种肿瘤类型中，人们已经研究了癌症患者中活跃但功能失调的免疫反应，但由于癌症理论的异质性，常见反应机制的理论似乎已经过时。在对癌症患者的已发表临床研究的综述中，检查了以下细胞因子的表达和相互作用：白细胞介素 2、白细胞介素 6、白细胞介素 8、白细胞介素 10、白细胞介素 12、白细胞介素 18、肿瘤坏死因子 α（TNFα）、转化生长因子 β（TGFβ）、干扰素-γ、HLA-DR、巨噬细胞移动抑制因子（MIF）和 C-X-C 基序趋化因子受体 4（CXCR4）。临床数据以非定量描述性方式进行分析，并根据实验中建立的生理细胞因子相互作用进行解释。出现的临床细胞因子模式表明，癌症患者同时发生免疫刺激和免疫抑制，MIF、TNFα、白细胞介素 6、白细胞介素 8、白细胞介素 10、白细胞介素 18 和 TGFβ 的浓度增加。这种特定的细胞因子模式似乎具有预后作用，因为在独立的癌症类型中，高白细胞介素 6 或白细胞介素 10 血清浓度与负面预后相关。尽管免疫刺激性细胞因子参与局部癌症相关炎症，但细胞因子介导的局部免疫抑制和由此产生的白细胞介素 12-干扰素-γ-HLA-DR 轴缺陷似乎使癌细胞免受免疫消除。肿瘤产生的细胞因子可能在这种缺陷中起关键作用。一个工作假设是，癌症特异性和组织学独立性的统一细胞因子级联是潜在副肿瘤系统性疾病的表现之一，这个假设将癌症阶段与免疫系统的功能状态和患者的预后联系起来。中和这种细胞因子模式可能为癌症提供新的、迄今为止尚未开发的治疗方法。
