RNF43 p.G659fs 通过 PI3K/AKT/mTOR 信号通路和 HLA-E 上调导致 MSI-high 结直肠癌中 NK 细胞功能障碍
RNF43 p.G659fs leads to natural killer cell dysfunction in MSI-high colorectal cancer through PI3K/AKT/mTOR signaling and HLA-E up-regulation.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Preoperative malnutrition is associated with suppressed intratumoral T cell function and distinct tumor-associated microbiota in colorectal cancer: a prospective pilot study.
Preoperative malnutrition is associated with suppressed intratumoral T cell function and distinct tumor-associated microbiota in colorectal cancer: a prospective pilot study.
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这些发现提示 CRC 患者中营养不良、肠道微生物群组成与抗肿瘤免疫抑制之间存在关联。
癌症相关营养不良显著降低治疗效果、降低化疗耐受性并损害免疫治疗疗效。使用营养不良通用筛查工具(MUST)等工具监测营养状况可能改善临床结局。营养不良还深刻影响免疫系统功能和肠道微生物群组成。然而,术前营养状况、抗肿瘤免疫与肿瘤相关微生物群之间的关系仍知之甚少。
我们前瞻性纳入了2017年7月至2021年8月期间在米兰IRCCS Ca' Granda Ospedale Maggiore Policlinico接受切除术的43例结直肠癌(CRC)患者。对患者进行了生化、人体测量学和营养状况评估,以及瘤内免疫表型和肿瘤相关微生物群评估。对8例有黏膜样本的患者(5例营养不良和3例非营养不良)进行了肿瘤相关微生物群分析。
营养不良与组织浸润性中性粒细胞增多以及T细胞表型改变相关,包括经典辅助性T细胞和iNKT细胞中效应相关细胞因子表达减少。肠道微生物群分析显示,中性粒细胞与淋巴细胞比值(NLR)与拟杆菌属、普雷沃菌属和副拟杆菌属之间存在显著关联,提示这些微生物可能在塑造营养不良个体免疫反应中发挥作用。
We prospectively enrolled 43 colorectal cancer (CRC) patients who underwent resection surgery between July 2017 and August 2021 at IRCCS Ca' Granda Ospedale Maggiore Policlinico in Milan. Patients were evaluated for biochemical, anthropometric, and nutritional profiles, as well as intratumoral immune phenotypes and tumor-associated microbiota. Tumor-associated microbiota analysis was performed in a subset of 8 patients (5 malnourished and 3 non-malnourished) for whom mucosal samples were available.
Malnutrition was associated with increased tissue-infiltrating neutrophils and altered T cell phenotypes, including reduced expression of effector-associated cytokines in conventional T-helper and iNKT cells. Gut microbiota analysis revealed significant associations between neutrophil lymphocyte ratio (NLR) and the bacterial genera Bacteroides , Prevotella , and Parabacteroides , suggesting a potential role for these microbes in shaping immune responses in malnourished individuals. DISCUSSION: These findings suggest a link between malnutrition, gut microbiota composition, and suppressed anti-tumor immunity in CRC patients.
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