CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题：Identification of a risk model for prognostic and therapeutic prediction in renal cell carcinoma based on infiltrating M0 cells.
Identification of a risk model for prognostic and therapeutic prediction in renal cell carcinoma based on infiltrating M0 cells.
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肿瘤微环境（TME）包括与肿瘤发展密切相关的免疫浸润细胞。通过筛选和分析与肿瘤浸润M0细胞相关的基因，我们开发了一个风险模型，为透明细胞肾细胞癌（ccRCC）提供治疗和预后指导。首先，分析了每种免疫细胞类型的浸润丰度及其与患者预后的相关性。在评估免疫细胞浸润深度与预后之间的潜在联系后，我们筛选了浸润性M0细胞，建立了一个以三个关键基因（TMEN174、LRRC19和SAA1）为中心的风险模型。相关性分析表明，风险评分与肿瘤免疫周期的多个阶段（包括B细胞募集）呈正相关。
此外，风险评分与CD8表达及多个热门免疫检查点（ICs）（TIGIT、CTLA4、CD274、LAG3和PDCD1）呈正相关。
另外，高风险组（HRG）的肿瘤免疫功能障碍和排斥（TIDE）评分及排斥评分均高于低风险组（LRG）。重要的是，风险评分与免疫治疗相关通路富集评分呈负相关，且LRG显示出比HRG更大的治疗获益。分析了HRG和LRG对靶向药物敏感性的差异。对于RCC常用靶向药物，包括axitinib、pazopanib、temsirolimus和sunitinib，LRG的IC50值较低，表明敏感性增加。
最后，66例石蜡包埋标本的免疫组化结果表明，SAA1在肿瘤样本中强表达，并与肿瘤转移、分期和分级相关。SAA1通过实验验证被发现具有显著的促肿瘤作用。
总之，这些数据证实了肿瘤浸润性M0细胞在ccRCC患者的预后和治疗中发挥关键作用。这一发现为ccRCC的预后预测和治疗提供了新的见解和方向。
The tumor microenvironment (TME) comprises immune-infiltrating cells that are closely linked to tumor development. By screening and analyzing genes associated with tumor-infiltrating M0 cells, we developed a risk model to provide therapeutic and prognostic guidance in clear cell renal cell carcinoma (ccRCC). First, the infiltration abundance of each immune cell type and its correlation with patient prognosis were analyzed.
After assessing the potential link between the depth of immune cell infiltration and prognosis, we screened the infiltrating M0 cells to establish a risk model centered on three key genes (TMEN174, LRRC19, and SAA1). The correlation analysis indicated a positive correlation between the risk score and various stages of the tumor immune cycle, including B-cell recruitment.
Furthermore, the risk score was positively correlated with CD8 expression and several popular immune checkpoints (ICs) (TIGIT, CTLA4, CD274, LAG3, and PDCD1).
Additionally, the high-risk group (HRG) had higher scores for tumor immune dysfunction and exclusion (TIDE) and exclusion than the low-risk group (LRG).
Importantly, the risk score was negatively correlated with the immunotherapy-related pathway enrichment scores, and the LRG showed a greater therapeutic benefit than the HRG. Differences in sensitivity to targeted drugs between the HRG and LRG were analyzed. For commonly used targeted drugs in RCC, including axitinib, pazopanib, temsirolimus, and sunitinib, LRG had lower IC50 values, indicating increased sensitivity.
Finally, immunohistochemistry results of 66 paraffin-embedded specimens indicated that SAA1 was strongly expressed in the tumor samples and was associated with tumor metastasis, stage, and grade. SAA1 was found to have a significant pro-tumorigenic effect by experimental validation. In summary, these data confirmed that tumor-infiltrating M0 cells play a key role in the prognosis and treatment of patients with ccRCC. This discovery offers new insights and directions for the prognostic prediction and treatment of ccRCC.
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