Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA.
Department of Medicine, Division of Hematology/Oncology, UCSF, San Francisco, California, USA.
J Clin Invest. 2024 Oct 15;134(20):e184310. doi: 10.1172/JCI184310.
The precise conditions by which cytokines drive cancer is relevant to improving immune checkpoint inhibition (ICI) responses while decreasing toxicity. In this issue of the JCI, Kao et al. investigated T helper cell pathways in patients with solid tumors receiving ICI. The authors evaluated T cell populations, cytokine signatures, immune related adverse events (irAEs), and survival outcomes. Patients with a history of autoimmune disorders were more likely to develop irAEs. Notably, blood samples from patients on treatment showed that elevations in IL-5, IL-6, IL-17f, and TNF-α were associated with an increased risk for grade 2 or higher irAEs. Moreover, IL-6 was associated with decreased objective response rate and worse cancer-specific and all-cause mortality. These findings may help guide decisions for optimizing ICI efficacy while minimizing toxicity and suggest that IL-6 blockade may improve response and decrease toxicity in solid tumors.
细胞因子促使癌症发生的确切条件与提高免疫检查点抑制（ICI）反应的同时降低毒性有关。在本期 JCI 中，Kao 等人研究了接受 ICI 的实体瘤患者的辅助性 T 细胞途径。作者评估了 T 细胞群、细胞因子特征、免疫相关不良事件（irAEs）和生存结果。有自身免疫性疾病病史的患者更容易发生 irAEs。值得注意的是，正在接受治疗的患者的血液样本表明，IL-5、IL-6、IL-17f 和 TNF-α 的升高与 2 级或更高级别的 irAEs 风险增加相关。此外，IL-6 与客观缓解率降低以及癌症特异性和全因死亡率恶化相关。这些发现可能有助于指导决策，以优化 ICI 的疗效，同时最大限度地降低毒性，并表明 IL-6 阻断可能改善实体瘤的反应并降低毒性。
