预测晚期结直肠癌患者接受新辅助化疗的高危因素中,CD274(PD-L1)和CD3+淋巴细胞的临床作用。
Clinical role of CD274 (PD-L1) and CD3+ lymphocytes in predicting high risk in advanced colorectal cancer patients receiving neoadjuvant chemotherapy.
发表日期:2023
作者:
Suat Benek, Mehmet Zengin
来源:
Cell Death & Disease
摘要:
癌症研究中,对肿瘤免疫反应机制的研究一直备受关注。本研究中,我们调查了CD274(程序性细胞死亡配体1 - PD-L1)和CD3+肿瘤浸润淋巴细胞(TILs)在新辅助化疗治疗的晚期结直肠癌(CRC)患者预后中的作用。我们回顾性地检查了2008年至2018年间手术治疗的III/IV期CRC患者的原发肿瘤标本。我们发现这些生物标志物与pT分期(PD-L1,p = 0.020;CD3+TILs,p = 0.025)、肿瘤分级(PD-L1,p = 0.005;CD3+TILs,p = 0.004)、手术切缘阳性(PD-L1,p = 0.001;CD3+TILs,p = 0.001)、微卫星不稳定状态(MSI)(PD-L1,p < 0.001;CD3+TILs,p < 0.001)等有显著关联。我们还发现这些生物标志物是MSI的独立风险因素(PD-L1,OR = 1.84 [1.27-4.02],p = 0.003;CD3+TILs,OR = 1.92 [1.31-4.35],p = 0.008)。单变量分析结果显示高PD-L1、低CD3+TILs或两者同时存在的患者预后不良(PD-L1:RFS,p = 0.008,OS,p = 0.001;CD3+TILs:RFS,p = 0.003,OS,p = 0.005;PD-L1和CD3+TILs:RFS,p < 0.001,OS,p < 0.001)。多变量分析结果显示高PD-L1和低CD3+TILs的结合使用能更好地预测RFS和OS不良(PD-L1和CD3+TILs:RFS,风险比 - HR,= 2.85 [95% CI: 1.36-3.84],p < 0.001;OS,HR = 2.74 [1.32-3.71],p < 0.001)。我们还发现高PD-L1也是另一个独立的整体和无复发生存参数。我们的研究结果表明,在接受化疗的CRC患者中,高PD-L1和低CD3+TILs的组合可以可靠地预测不良预后,因此这些生物标志物可能在制定和执行适当的靶向治疗方案方面具有潜在价值。
In cancer research, the mechanism underlying the immune response to a tumour has been of great interest. In this study, we investigated the role of CD274 (programmed cell death-ligand 1 - PD-L1) and CD3+ tumour-infiltrating lymphocytes (TILs) in the prognosis of advanced colorectal cancer (CRC) patients treated with neoadjuvant chemotherapy. We retrospectively examined primary tumour specimens from stage III/IV CRC patients operated on between 2008 and 2018. We found a significant association between these biomarkers and pT stage (PD-L1, p = 0.020; CD3+TILs, p = 0.025), tumour grade (PD-L1, p = 0.005; CD3+TILs, p = 0.004), positive surgical margin (PD-L1, p = 0.001; CD3+TILs, p = 0.001), MSI (PD-L1, p < 0.001; CD3+TILs, p < 0.001), etc. We also discovered that these biomarkers are independent risk factors for MSI (PD-L1, OR = 1.84 [1.27-4.02], p = 0.003; CD3+TILs, OR = 1.92 [1.31-4.35], p = 0.008). Univariate analysis results revealed that patients with high PD-L1, low CD3+TIL, and both showed poor relapse-free survival (RFS) and poor overall survival (OS) (PD-L1: RFS, p = 0.008 and OS, p = 0.001; CD3+TILs: RFS, p = 0.003 and OS, p = 0.005; PD-L1 and CD3+TILs: RFS, p < 0.001 and OS, p < 0.001). The results of the multivariate analysis showed that the combined use of high PD-L1 and low CD3+TILs was a better predictor of poor RFS and OS (PD-L1 and CD3+TILs: RFS, hazard ratio - HR, = 2.85 [95% CI: 1.36-3.84], p < 0.001); OS, HR = 2.74 [1.32-3.71], p < 0.001). We also found a high PD-L1 parameter as another independent overall and relapse-free survival parameter. Our findings suggest that a combination of high PD-L1 and low CD3+TIL can reliably predict poor survival in CRC patients receiving chemotherapy. Therefore, these biomarkers may be promising for the planning and execution of appropriate targeted therapies.