Zhang Lingbing, Bonomi Philip D
Yinuoke Ltd., Changchun 130012, China.
Division of Hematology/Oncology, Rush University Medical Center, Chicago, IL 60612, USA.
Cancers (Basel). 2024 Apr 27;16(9):1709. doi: 10.3390/cancers16091709.
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流失为特征的衰弱性疾病，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和临床研究中CAC与抗癌免疫反应之间的潜在关系。临床前研究表明，白细胞介素-1β、白细胞介素-6、白细胞介素-8、干扰素-γ、肿瘤坏死因子-α和转化生长因子-β等细胞因子参与了CAC。白细胞介素-6和肿瘤坏死因子-α与肌肉和脂肪组织相互作用，通过JAK/STAT和NF-κB途径诱导消瘦。髓源性抑制细胞（MDSCs）通过促进炎症加剧CAC。临床研究证实，CAC患者的促炎细胞因子（白细胞介素-6、白细胞介素-8、肿瘤坏死因子α）和免疫标志物如中性粒细胞与淋巴细胞比值（NLR）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机制可增强抗癌治疗，尤其是免疫治疗。新型免疫调节剂R-酮咯酸可逆转小鼠体重减轻并提高生存率。将这些药物与免疫治疗联合使用可能使患有CAC的癌症患者受益。进一步的研究对于理解免疫治疗期间肿瘤诱导的免疫失调与CAC之间的复杂相互作用至关重要。
