Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Yeouido St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Yeouido St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
Cytokine. 2021 Feb;138:155363. doi: 10.1016/j.cyto.2020.155363. Epub 2020 Nov 29.
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.
对于免疫治疗的明确适应证，寻找能够预测治疗反应的合适生物标志物是必要的。炎症细胞因子在针对感染源或癌细胞的免疫反应中发挥着关键作用，被认为可以在免疫检查点抑制剂（ICI）启动后激活免疫细胞。通过激活 T 细胞、自然杀伤细胞、巨噬细胞或肿瘤浸润树突状细胞等免疫细胞，炎症细胞因子通常在 PD-1/PD-L1 轴阻断后增加。已经有几项研究评估了接受免疫治疗的非小细胞肺癌（NSCLC）患者中炎症细胞因子早期变化的预测价值。在这篇迷你综述中，我们查阅了最近关于 NSCLC 患者接受 ICI 治疗时血液中炎症细胞因子潜在水平值及其在开始接受 ICI 治疗前后早期变化的文章，以预测对治疗的反应和疾病进展。这些研究评估了细胞因子，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，以预测对 ICI 的反应。细胞因子组合面板有助于预测接受 ICI 治疗的 NSCLC 患者的反应和预后。此外，如果能够预测反应和肿瘤负荷的变化，将提供更个体化的 ICI 治疗。然而，接受 ICI 的 NSCLC 患者的细胞因子研究大多数患者数量较少，且测量时间点存在异质性。尽管如此，IL-8 和 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。为了将血液细胞因子水平用作免疫治疗的生物标志物，需要进行一项具有统一测量方案的更大规模研究。
