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:Immune Profile of Blood, Tissue and Peritoneal Fluid: A Comparative Study in High Grade Serous Epithelial Ovarian Cancer Patients at Interval Debulking Surgery.
Immune Profile of Blood, Tissue and Peritoneal Fluid: A Comparative Study in High Grade Serous Epithelial Ovarian Cancer Patients at Interval Debulking Surgery.
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高级别浆液性卵巢上皮癌(HGSOC)是一种免疫原性肿瘤,其独特肿瘤微环境(TME)延伸至腹膜腔。TME 的免疫抑制特性是开发 HGSOC 有效治疗方案的主要挑战,其中免疫细胞之间的相互作用十分重要。
因此,深入了解 TME 免疫谱可能有助于探索替代治疗方案。研究者采用流式细胞术、ELISA 和 Procartaplex 免疫检测,对腹水、肿瘤标本和血液进行免疫谱分析。腹水中 CD56^bright NK 细胞频率及功能性受体表达降低;活化型 NKp46⁺CD56^dim NK 细胞增加,可能提示腹水中的抗肿瘤反应存在差异。肿瘤标本中 NK、NKT 样及 T 细胞的功能性受体下降更为显著。腹水中可溶性配体 MIC-B 和 PVR 减少,而 B7-H6 增加;肿瘤细胞播散会促成腹水中可溶性配体的存在。血清和腹水的细胞因子谱不同:IL-2、IL-8、IL-15、IL-27、IFN-γ 和 GM-CSF 在腹水中特异性升高。
综上,差异性免疫谱以及可溶性指标、NK 细胞受体与化疗应答评分之间的相关性,可增进对抗肿瘤免疫反应的认识,并助力开发有效治疗方式。
High-grade serous epithelial ovarian carcinoma (HGSOC) is an immunogenic tumor with a unique tumor microenvironment (TME) that extends to the peritoneal cavity. The immunosuppressive nature of TME imposes the major challenge to develop effective treatment options for HGSOC. Interaction of immune cells in TME is an important factor. Hence, a better understanding of immune profile of TME may be required for exploring alternative treatment options. Immune profiling of peritoneal fluid (PF), tumor specimens, and blood were carried out using flowcytometry, ELISA, and Procartaplex immunoassay.
The frequency of CD56 Bright NK cells and expression of functional receptors were reduced in PF. Increased activating NKp46+CD56 Dim NK cells may indicate differential antitumor response in PF. Functional receptors on NK, NKT-like and T cells were reduced more drastically in tumor specimens.
Soluble ligands MIC-B and PVR were reduced, whereas B7-H6 was increased in PF. Dissemination of tumor cells contributes to soluble ligands in PF. A differential cytokine profile was found in serum and PF as IL-2, IL-8, IL-15, IL-27, IFN- , and GM-CSF were elevated specifically in PF.
In conclusion, the differential immune profile and correlation of soluble parameters and NK cell receptors with chemo response score may add knowledge to understand anti-tumor immune response to develop effective treatment modality.
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