CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Mast Cell Infiltration and Subtype Promote Malignant Transformation of Oral Precancer and Progression of Oral Cancer.
Mast Cell Infiltration and Subtype Promote Malignant Transformation of Oral Precancer and Progression of Oral Cancer.
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肥大细胞(MC)是一种常见的髓系来源免疫细胞,其在口腔鳞状细胞癌(OSCC)发生发展中的作用尚不明确。本研究旨在探讨MC在口腔癌前病变和口腔癌中的浸润情况。利用RNA测序和多个公共数据集评估OSCC中免疫细胞浸润及其与预后的关系。采用多重免疫荧光技术探讨MC在OSCC和口腔癌前病变微环境中的浸润情况及其与CD8+细胞的相互作用。通过体内实验验证MC在OSCC进展中的作用。静息态MC浸润主要存在于口腔癌前病变中,而活化态MC浸润在OSCC中显著更高。活化态MC与口腔癌前病变的恶性转化及OSCC的不良预后相关。体内研究显示MC可促进OSCC的生长。活化态MC的浸润与CD8+ T细胞的浸润呈负相关。含类胰蛋白酶而不含糜蛋白酶的MC亚型(MCT)在OSCC中显著高于口腔癌前病变,并与不良生存相关。此外,空间距离分析显示MCT与CD8+细胞之间的距离更大,这也与OSCC的不良预后相关。Cox回归分析显示MCT可能是潜在的诊断和预后生物标志物。本研究为MC在OSCC免疫微环境中的作用提供了新见解。通过开发针对MC的靶向治疗,可能提高OSCC的免疫治疗效果。意义:在本研究中,我们探讨了肥大细胞(MC)在口腔癌前病变和口腔癌中的作用,并证明MCs参与口腔癌进展,可能作为潜在的诊断和预后标志物。通过开发针对MCs的靶向治疗,可能提高免疫治疗疗效。
UNLABELLED: The role of mast cell (MC), a common myeloid-derived immune cell, in the development of oral squamous cell carcinoma (OSCC) is unclear. The aim of this study was to investigate MC infiltration in oral precancer and oral cancer. The evaluation of immune cell infiltration and its association with prognosis in OSCC used RNA sequencing and multiple public datasets. Multiplex immunofluorescence was used to explore the infiltration of MC in the microenvironment of OSCC and oral precancer and the interaction with CD8+ cells. The role of MC in OSCC progression was verified by in vivo experiments.
The resting MC infiltration was mainly present in oral precancer, whereas activated MC infiltration was significantly higher in OSCC. Activated MC was associated with malignant transformation of oral precancer and poor prognosis of OSCC. In vivo studies showed that MC promoted the growth of OSCC. The infiltration of activated MC was negatively correlated with the infiltration of CD8+ T cells. The subtype of MC containing tryptase without chymase (MCT) was significantly higher in OSCC compared with oral precancer and was associated with poor survival.
Furthermore, spatial distance analysis revealed a greater distance between MCT and CD8+ cells, which was also linked to poor prognosis in OSCC. Cox regression analysis showed that MCT could be a potential diagnostic and prognostic biomarker.
This study provides new insights into the role of MC in the immune microenvironment of OSCC. It might enhance the immunotherapeutic efficacy of OSCC by developing targeted therapies against MC. SIGNIFICANCE: In this study, we investigated the role of mast cells (MC) in oral precancer and oral cancer and demonstrated that MCs are involved in oral cancer progression and may serve as a potential diagnostic and prognostic marker. It might improve the immunotherapeutic efficacy through developing targeted therapies against MCs.
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