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
单药双特异性抗 PD-L1/TGF-β抗体与化疗协同作为胰腺导管腺癌新辅助治疗：一项临床前实验研究
英文原题：Single dual-specific anti-PD-L1/TGF-β antibody synergizes with chemotherapy as neoadjuvant treatment for pancreatic ductal adenocarcinoma: a preclinical experimental study.
查看英文原题
Single dual-specific anti-PD-L1/TGF-β antibody synergizes with chemotherapy as neoadjuvant treatment for pancreatic ductal adenocarcinoma: a preclinical experimental study.
分数与星级只用于站内排序 —— 不代表疗效、安全性或个人适用性。
研究概要
我们的结果表明，BiTP 联合化疗是一种有前景的 PDAC 新辅助治疗方法。
研究思路结论见上方概要
目的
化疗耐药是胰腺导管腺癌（PDAC）新辅助治疗失败的重要原因。BiTP（抗PD-L1/TGF-β双特异性抗体）是一种单一抗体，可同时双重靶向转化生长因子-β（TGF-β）和程序性细胞死亡配体1（PD-L1）。本研究试图探讨BiTP联合一线化疗在PDAC中的疗效。
方法
BiTP联合吉西他滨和白蛋白结合型紫杉醇的临床前评估通过可切除KPC小鼠模型（C57BL/6J）完成。采用光谱流式细胞术、组织切片染色、酶联免疫吸附试验、Counting Kit-8、transwell和Western blot试验研究协同效应。
结果
BiTP联合化疗在新辅助治疗中显著降低了PDAC肿瘤分期，提高了生存率，并使PDAC小鼠具有更高的可切除性。BiTP与靶点高亲和力结合，逆转了PDAC细胞的化疗耐药性。该联合方案通过增加T细胞、NK 细胞和树突状细胞的浸润和功能，并降低免疫抑制相关细胞如调节性T细胞、M2巨噬细胞、髓源性抑制细胞和癌症相关成纤维细胞的功能，重编程肿瘤微环境，从而克服了免疫逃逸。
展开英文摘要原文
METHODS
Preclinical assessments of BiTP plus gemcitabine and nab-paclitaxel were completed through a resectable KPC mouse model (C57BL/6J). Spectral flow cytometry, tissue section staining, enzyme-linked immunosorbent assays, Counting Kit-8, transwell, and Western blot assays were used to investigate the synergistic effects.
RESULTS
BiTP combinatorial chemotherapy in neoadjuvant settings significantly downstaged PDAC tumors, enhanced survival, and had a higher resectability for mice with PDAC. BiTP was high affinity binding to targets and reverse chemotherapy resistance of PDAC cells. The combination overcame immune evasion through reprogramming tumor microenvironment via increasing penetration and function of T cells, natural killer cells, and dendritic cells and decreasing the function of immunosuppression-related cells as regulatory T cells, M2 macrophages, myeloid-derived suppressor cells, and cancer-associated fibroblasts.
CONCLUSION
Our results suggest that the BiTP combinatorial chemotherapy is a promising neoadjuvant therapy for PDAC.
论文信息
- 作者
- Zhang H、Chen J、Bai J、Zhang J、Huang S、Zeng L、Zhou P、Shen Q
- 单位
- Department of Pancreatic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan.China
- 期刊
- International journal of surgery (London, England)2024 May 1
- 原文标识
- PubMed 38489548 · DOI 10.1097/JS9.0000000000001226
在 PubMed 查看 → 出版商原文（DOI） 全文 PDF（PMC）· 可下载 治疗专题与资料阅读指南 资料来源与翻译说明 报告译文或资料问题 →