For a definite indication for immunotherapy, finding appropriate biomarkers that are predictive of treatment responses is necessary. Inflammatory cytokines which play critical roles in immunity against infectious sources or cancer cells are suggested to activate immune cells after initiation of immune checkpoint inhibitors (ICI). Through activation of immune cells such as T cells, natural killer cells, macrophages, or tumor infiltrating dendritic cells, inflammatory cytokines usually increase after programmed death (PD)-1/PD-L1 axis blockade. There have been several studies evaluating the predictive value of early changes in inflammatory cytokines in non-small cell lung cancer (NSCLC) patients undergoing immunotherapy. In this mini-review, we went through recent articles on potential blood level values of inflammatory cytokines in NSCLC patients receiving ICI and their early change around commencement of ICIs in predicting response to treatment and disease progression. The studies evaluated cytokines including interleukin (IL)-2, 6, 8, interferon (IFN)-γ, and tumor necrosis factor (TNF)-α for predictability for responses to ICI. A combination cytokine panel can help predict the response and prognosis of patients with NSCLC who are receiving ICI treatment. Furthermore, a more individualized ICI treatment will be available if responses and change in tumor burden can be predicted. However, most of the studies on cytokines in NSCLC patients receiving ICIs had a small number of patients, and the heterogeneous measurement time points. Nevertheless, cytokines such as IL-8 and IFN- γ have considerable potential predictive value for immunotherapy response, which is worthy of further studies. To utilize blood cytokines levels as biomarkers for immunotherapy, a larger study with uniform measurement protocol is necessary.

中文翻译：

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晚期非小细胞肺癌患者使用免疫检查点抑制剂后炎性细胞因子水平变化的潜在预测价值

对于免疫治疗的明确适应症，有必要找到可预测治疗反应的合适生物标志物。建议在免疫检查点抑制剂 (ICI) 启动后，在针对感染源或癌细胞的免疫中起关键作用的炎性细胞因子激活免疫细胞。通过激活 T 细胞、自然杀伤细胞、巨噬细胞或肿瘤浸润性树突状细胞等免疫细胞，炎症细胞因子通常在程序性死亡 (PD)-1/PD-L1 轴阻断后增加。有几项研究评估了接受免疫治疗的非小细胞肺癌 (NSCLC) 患者炎症细胞因子早期变化的预测价值。在这个迷你评论中，我们浏览了最近关于接受 ICI 的 NSCLC 患者中炎性细胞因子的潜在血液水平值及其在 ICI 开始时的早期变化以预测对治疗和疾病进展的反应的文章。这些研究评估了包括白细胞介素 (IL)-2、6、8、干扰素 (IFN)-γ 和肿瘤坏死因子 (TNF)-α 在内的细胞因子对 ICI 反应的可预测性。联合细胞因子面板可以帮助预测接受 ICI 治疗的 NSCLC 患者的反应和预后。此外，如果可以预测肿瘤负荷的反应和变化，则将提供更加个性化的 ICI 治疗。然而，大多数关于接受 ICIs 的 NSCLC 患者细胞因子的研究的患者数量较少，且测量时间点存在异质性。尽管如此，IL-8、IFN-γ等细胞因子对免疫治疗反应具有相当大的潜在预测价值，值得进一步研究。为了利用血液细胞因子水平作为免疫治疗的生物标志物，需要进行具有统一测量方案的更大规模研究。