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:Isolation and Phenotypic Characterization of Tumor-Infiltrating NK Cells in Skin Carcinoma.
Isolation and Phenotypic Characterization of Tumor-Infiltrating NK Cells in Skin Carcinoma.
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在肿瘤学研究中,肿瘤浸润性自然杀伤(NK)细胞在皮肤癌中的功能为新型治疗方法提供了一条可行途径。NK细胞是机体防御恶性肿瘤(包括皮肤癌)所必需的,在更复杂的癌症免疫疗法(如含有树突状细胞的疫苗)中尤为重要。最致命的皮肤癌类型——恶性黑色素瘤,即使早期治疗取得了进展,其预后仍然很差,这凸显了对新型治疗策略的需求。对人黑色素瘤转移灶中的NK细胞进行单细胞RNA-seq分析,结果显示肿瘤浸润性和循环NK细胞的转录程序存在显著差异。已侵入肿瘤的NK细胞表现出不同的转录状态,表明它们在趋化因子产生和细胞毒性等领域具有功能特化。这些结果强调了NK细胞在招募其他重要免疫细胞类型(如交叉呈递树突状细胞)以及直接杀伤恶性细胞方面的功能。研究浸润皮肤癌肿瘤的NK细胞,为理解并可能改造这些癌症周围的免疫环境提供了一条可行途径。了解NK细胞在肿瘤微环境中的独特特征和作用,对于开发更有效的免疫治疗方法以治疗皮肤癌至关重要。为了可能为癌症免疫治疗开辟新方向,本项目旨在建立一种用于分离皮肤癌中肿瘤浸润性NK细胞并进行全面表型表征的完善技术。
In oncological research, the function of tumor-infiltrating natural killer (NK) cells in skin carcinoma presents a viable avenue for novel therapeutic methods. NK cells are essential to the body's defense against malignancies, including skin cancer, and are especially important in more sophisticated cancer immunotherapies such as vaccinations containing dendritic cells. The deadliest type of skin cancer, malignant melanoma, still has a poor prognosis even with advancements in early-stage therapies, which emphasizes the need for novel therapeutic strategies. NK cells from human melanoma metastases were subjected to single-cell RNA-seq analysis, which demonstrated notable variations in the transcriptional programs of tumor-infiltrating and circulating NK cells. Different transcriptional states are displayed by NK cells that have invaded tumors, indicating that they are functionally specialized in areas like chemokine production and cytotoxicity.
These results emphasize the functions of NK cells in recruiting other significant immune cell types, such as cross-presenting dendritic cells, and in direct cytotoxicity against malignant cells. Investigating NK cells that infiltrate tumors in skin carcinomas presents a viable approach to comprehending and may be modifying the immune environment surrounding these cancers.
It is essential to comprehend the distinct characteristics and roles of NK cells inside the tumor microenvironment in order to create more potent immunotherapeutic approaches to treat skin cancer. In order to perhaps open the door for new directions in cancer immunotherapy, the project intends to establish a thorough technique for the isolation and thorough phenotypic characterization of tumor-infiltrating NK cells in skin carcinoma.
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