Cancer-associated cachexia (CAC) is a debilitating condition marked by muscle and fat loss, that is unresponsive to nutritional support and contributes significantly to morbidity and mortality in patients with cancer. Immune dysfunction, driven by cytokine imbalance, contributes to CAC progression. This review explores the potential relationship between CAC and anti-cancer immune response in pre-clinical and clinical studies. Pre-clinical studies showcase the involvement of cytokines like IL-1β, IL-6, IL-8, IFN-γ, TNF-α, and TGF-β, in CAC. IL-6 and TNF-α, interacting with muscle and adipose tissues, induce wasting through JAK/STAT and NF-κB pathways. Myeloid-derived suppressor cells (MDSCs) exacerbate CAC by promoting inflammation. Clinical studies confirm elevated pro-inflammatory cytokines (IL-6, IL-8, TNFα) and immune markers like the neutrophil-to-lymphocyte ratio (NLR) in patients with CAC. Thus, immunomodulatory mechanisms involved in CAC may impact the anti-neoplastic immune response. Inhibiting CAC mechanisms could enhance anti-cancer therapies, notably immunotherapy. R-ketorolac, a new immunomodulator, reversed the weight loss and increased survival in mice. Combining these agents with immunotherapy may benefit patients with cancer experiencing CAC. Further research is vital to understand the complex interplay between tumor-induced immune dysregulation and CAC during immunotherapy.
癌症相关性恶病质（CAC）是一种以肌肉和脂肪消耗为特征的衰弱状态，对营养支持无反应，并显著增加癌症患者的发病率和死亡率。由细胞因子失衡驱动的免疫功能障碍促进了CAC的进展。本综述探讨了临床前及临床研究中CAC与抗癌免疫反应之间的潜在关联。临床前研究表明，IL-1β、IL-6、IL-8、IFN-γ、TNF-α和TGF-β等细胞因子参与CAC的发生发展。其中IL-6和TNF-α通过与肌肉及脂肪组织相互作用，经JAK/STAT和NF-κB通路诱导消耗状态。髓源性抑制细胞（MDSCs）则通过促进炎症反应加剧CAC。临床研究证实，CAC患者体内促炎细胞因子（IL-6、IL-8、TNFα）及中性粒细胞与淋巴细胞比值（NLR）等免疫标志物水平升高。因此，参与CAC的免疫调节机制可能影响抗肿瘤免疫反应。抑制CAC机制有望增强抗癌治疗效果，特别是在免疫治疗领域。新型免疫调节剂R-酮咯酸在小鼠实验中成功逆转体重下降并提高生存率。将此类药物与免疫疗法联用，或可为经历CAC的癌症患者带来获益。未来需进一步研究以阐明免疫治疗过程中肿瘤诱导的免疫失调与CAC之间复杂的相互作用机制。
肿瘤(癌症)患者之家