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:Complete Response in Recurrent End-Stage Pancreatic Cancer After Combined Immune Cell Therapy of α-Galactosylceramide Dendritic Cell Vaccine Therapy, Wilms' Tumor 1 Dendritic Cell Vaccine and Natural Killer Cell Therapy.
Complete Response in Recurrent End-Stage Pancreatic Cancer After Combined Immune Cell Therapy of α-Galactosylceramide Dendritic Cell Vaccine Therapy, Wilms' Tumor 1 Dendritic Cell Vaccine and Natural Killer Cell Therapy.
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胰腺癌死亡率和发病负担均高,复发后预后更差。化疗或放疗等现行标准治疗对复发性终末期胰腺癌疗效有限。一名70多岁男性因复发性终末期胰腺癌(分期未注明),并有肠系膜和气管旁淋巴结及右肝叶多发转移,来到我院就诊。由于副作用严重,患者已无法继续化疗。单采后,患者开始接受联合免疫细胞疗法,包括加入α-半乳糖神经酰胺(α-GalCer)负载树突状细胞(DC)疫苗治疗、WT1疫苗及自然杀伤(NK)细胞治疗。近3个月内每种疗法各实施7次后,随访正电子发射断层显像-计算机断层扫描(PET-CT)显示复发癌灶及转移灶均缩小。期间未给予化疗。肿瘤相关标志物显著下降(CA19-9由88.3降至54.4 U/mL;DU-PAN-2由267降至76 U/mL),免疫谱状态改善(中性粒细胞比例由68%降至64.2%;淋巴细胞比例由18%升至25.6%;中性粒细胞/淋巴细胞比值由3.8降至2.5)。患者体能状态起初恶化至1或2级,后恢复至0级,无残疾且日常生活不受限。未记录到与免疫细胞疗法相关的不良事件或副作用。本病例报告显示,将α-GalCer DC疫苗治疗整合进WT1疫苗和NK细胞治疗,可能增强免疫细胞疗法抗肿瘤作用,具有临床潜力。尽管病例报告为后续研究提供了重要启示,仍需进一步观察和研究,最终以改善晚期癌症患者结局。
Pancreatic cancer exhibits high mortality and morbidity, and the prognosis worsens when recurrence occurs. Current standard treatments, such as chemotherapy or radiation, show limited efficacy in recurrent end-stage pancreatic cancer. A man in his 70s visited our facility with a diagnosis of recurrent end-stage pancreatic cancer (Stage ) with multiple metastases to mesenteric and paratracheal lymph nodes and the right liver lobe. Due to the severe side effects, chemotherapy was not an option anymore. After apheresis, a combined immune cell-based therapy incorporating -galactosylceramide ( -Galcer)-pulsed dendritic cell (DC) vaccine therapy into Wilms' tumor 1 (WT-1) vaccine and natural killer (NK) cell therapy was initiated. On completing a nearly three-month course of seven administrations of each therapy, follow-up positron emission tomography-computed tomography (PET-CT) scans showed the regression of the recurrent cancer region as well as the metastasis regions. Meanwhile, chemotherapy was not provided.
A significant decrease in tumor-associated markers (i. e. , CA19-9, from 88. 3 to 54. 4 U/mL; DU-PAN-2, from 267 to 76 U/mL) and improvement in the immune profile status (i. e. , neutrophil percentage decreased from 68% to 64. 2%; lymphocyte percentage increased from 18% to 25. 6%, and neutrophil-lymphocyte ratio decreased from 3. 8 to 2. 5) were observed. His performance status initially deteriorated (to 1 or 2), but improved to 0 without any disability and limiting daily life.
Any adverse events or side effects associated with the immune cell-based therapy were not recorded. This single-patient case report demonstrated the clinical potential of incorporating -Galcer DC vaccine therapy into WT-1 vaccine and NK cell therapy to enhance the anti-tumor effects of immune cell-based therapy. While this case report provided significant insights to facilitate future research, further observations and investigations are warranted with the ultimate goal of improving outcomes in patients with advanced cancers.
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