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:Impact of cytotoxic T lymphocytes immunotherapy on prognosis of colorectal cancer patients.
Impact of cytotoxic T lymphocytes immunotherapy on prognosis of colorectal cancer patients.
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淋巴转移(风险比[HR]=4.498,95% 置信区间[CI]:1.290-15.676;P=0.018)和较低的 HLA-I 表达(HR=0.294,95%CI:0.089-0.965;P=0.044)与 CTL 组较差的 OS 相关。rAAV-DCs 诱导的 CTLs 在 CRC 患者中可能达到与化疗相当的效果,肿瘤相关 HLA-I 表达高且无淋巴转移的病例更可能从 CTLs 中获益。
体外扩增和激活细胞毒性T淋巴细胞(CTLs)是一种有前景的免疫治疗策略,CTLs可由负载肿瘤相关抗原(TAAs)并经重组腺相关病毒(rAAV)转化的树突状细胞(DCs)致敏。本研究旨在探讨rAAV-DC诱导的CTLs对CRC预后的影响,并探索与预后相关的因素。
本前瞻性观察性研究纳入2016年至2019年在昆明医科大学附属延安医院接受CRC手术的患者。主要结局为无进展生存期(PFS),次要结局为总生存期(OS)和不良事件。共纳入49例,其中29例和20例分别接受rAAV-DC诱导的CTL和化疗。
随访37-69个月(中位54个月)后,两组OS(P=0.0596)和PFS(P=0.0788)相当。接受CTL输注的2例(6.9%)患者出现轻度发热。化疗组所有患者均出现轻至中度不良反应,包括血管炎(n=20,100%)、呕吐(n=5,25%)、恶心(n=17,85%)和乏力(n=17,85%)。
Expansion and activation of cytotoxic T lymphocytes (CTLs) in vitro represents a promising immunotherapeutic strategy, and CTLs can be primed by dendritic cells (DCs) loaded with tumor-associated antigens (TAAs) transformed by recombinant adeno-associated virus (rAAV). This study aimed to explore the impact of rAAV-DC-induced CTLs on prognosis of CRC and to explore factors associated with prognosis.
This prospective observational study included patients operated for CRC at Yan'an Hospital Affiliated to Kunming Medical University between 2016 and 2019. The primary outcome was progression-free survival (PFS), secondary outcomes were overall survival (OS) and adverse events. Totally 49 cases were included, with 29 and 20 administered rAAV-DC-induced CTL and chemotherapy, respectively.
After 37-69 months of follow-up (median, 54 months), OS (P=0.0596) and PFS (P=0.0788) were comparable between two groups. Mild fever occurred in 2 (6.9%) patients administered CTL infusion. All the chemotherapy group experienced mild-to-moderate adverse effects, including vasculitis (n=20, 100%), vomiting (n=5, 25%), nausea (n=17, 85%) and fatigue (n=17, 85%).
Lymphatic metastasis (hazard ratio [HR]=4.498, 95% confidence interval [CI]: 1.290-15.676; P=0.018) and lower HLA-I expression (HR=0.294, 95%CI: 0.089-0.965; P=0.044) were associated with poor OS in the CTL group. CTLs induced by rAAV-DCs might achieve comparable effectiveness in CRC patients compare to chemotherapy, cases with high tumor-associated HLA-I expression and no lymphatic metastasis were more likely to benefit from CTLs.
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