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:The effect of NK cell therapy on sepsis secondary to lung cancer: A case report.
The effect of NK cell therapy on sepsis secondary to lung cancer: A case report.
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脓毒症患者死亡率高、预后不佳,因此亟需先进治疗干预。一名男性患者被诊断为中低分化鳞状细胞癌,接受了多种治疗,包括放疗、化疗、免疫治疗及抑制血管生成的靶向治疗。综合治疗后患者发生脓毒症,常规抗生素联合方案无法有效控制感染。作为实验性治疗,患者接受了异体自然杀伤(NK)细胞输注。输注后患者恢复意识,实验室检查显示感染相关指标下降、血清炎症细胞因子受到抑制、抗肿瘤细胞因子升高。然而,治疗效果仅持续 2–3 天。体外研究显示,异体 NK 细胞产品可降低患者血清中的白细胞介素-6 水平。此外,将 NK 细胞产品与患者血清后续共培养,导致 NK 细胞毒性亚群比例降低,NK 介导杀伤分子的表达下调。总之,过继输注异体 NK 细胞可能改善肿瘤相关脓毒症患者的脓毒症症状;体外共培养检测有望为治疗效果提供预测性生物标志物。
Patients with sepsis face high mortality rates and a bleak prognosis, prompting the need for advanced therapeutic interventions. A male patient diagnosed with moderately low-differentiated squamous cell carcinoma received diverse treatments, including radiotherapy, chemotherapy, immunotherapy, and targeted therapy to inhibit angiogenesis.
Subsequently, he developed sepsis after comprehensive treatment, and conventional antibiotic combinations proved ineffective in combating the infection. As an experimental approach, allogeneic natural killer (NK) cell infusion was administered. Following the NK cell infusion, the patient regained consciousness, and laboratory analyses showed reduced infection-related markers, suppressed serum inflammatory cytokines, and elevated anti-tumor cytokines.
However, the therapeutic effect only lasted 2-3 days. In vitro investigations demonstrated that the allogeneic NK cell product reduced interleukin-6 levels in the patient's serum.
Moreover, subsequent co-cultivation of the NK cell product with the patient's serum resulted in a decrease in the proportion of cytotoxic subpopulations of NK cells and a downregulation of the expression of NK-mediated killing molecules.
In conclusion, adoptive transfusion of allogeneic NK cells may improve sepsis symptoms in patients with tumor-related sepsis. In vitro co-culture tests hold promise in providing predictive biomarkers for treatment effectiveness.
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