Cachexia is a paraneoplastic syndrome that accompanies and compromises cancer treatment, especially in advanced stages, affecting the metabolism and function of several organs. The adipose tissue is the first to respond to the presence of the tumor, contributing to the secretion of factors which drive the systemic inflammation, a hallmark of the syndrome. While inflammation is a defensive innate response, the control mechanisms have been reported to be disrupted in cachexia. On the other hand, little is known about the role of NLRP3 inflammasome in this scenario, a multiprotein complex involved in caspase-1 activation and the processing of the cytokines IL-1β and IL-18.

based on the evidence from our previous study with a rodent model of cachexia, we examined the activation of the NLRP3 inflammasome pathway in two adipose tissue depots obtained from patients with colorectal cancer and compared with that another inflammatory pathway, NF-κB.

For CC we found opposite modulation in ScAT and PtAT for the gene expression of TLR4, Caspase-1 (cachectic group) and for NF-κB p50, NF-κB p65, IL-1β. CD36, expression was decreased in both depots while that of NLRP3 and IL-18 was higher in both tissues, as compared with controls and weight stable patients (WSC). Caspase-1 basal protein levels in the ScAT culture supernatant were higher in WSC and (weight stable patients) CC, when compared to controls. Basal ScAT explant culture medium IL-1β and IL-18 protein content in ScAT supernatant was decreased in the WSC and CC as compared to CTL explants.

The results demonstrate heterogeneous responses in the activation of genes of the NLRP3 inflammasome pathway in the adipose tissue of patients with cancer cachexia, rendering this pathway a potential target for therapy aiming at decreasing chronic inflammation in cancer.

恶病质是一种伴随和影响癌症治疗的副肿瘤综合征，尤其是在晚期阶段，会影响多个器官的代谢和功能。脂肪组织是第一个对肿瘤的存在做出反应的组织，有助于分泌驱动全身炎症的因子，这是该综合征的标志。虽然炎症是一种防御性的先天反应，但据报道控制机制在恶病质中被破坏。另一方面，NLRP3 炎症小体在这种情况下的作用知之甚少，这是一种参与 caspase-1 激活和细胞因子 IL-1β 和 IL-18 加工的多蛋白复合物。

基于我们之前对恶病质啮齿动物模型的研究的证据，我们检查了从结肠直肠癌患者获得的两个脂肪组织库中 NLRP3 炎症小体途径的激活，并与另一种炎症途径 NF-κB 进行了比较。

对于 CC，我们发现 ScAT 和 PtAT 对 TLR4、Caspase-1（恶病质组）和 NF-κB p50、NF-κB p65、IL-1β 的基因表达有相反的调节。与对照组和体重稳定的患者 (WSC) 相比，CD36 在两个库中的表达均降低，而 NLRP3 和 IL-18 在两种组织中的表达均较高。与对照相比，WSC 和（体重稳定的患者）CC 中 ScAT 培养上清液中的 Caspase-1 基础蛋白水平更高。与 CTL 外植体相比，WSC 和 CC 中 ScAT 上清液中的基础 ScAT 外植体培养基 IL-1β 和 IL-18 蛋白含量降低。

结果表明，癌症恶病质患者脂肪组织中 NLRP3 炎症小体通路基因的激活存在异质性反应，使该通路成为旨在减少癌症慢性炎症的潜在治疗靶点。