Background

Neoadjuvant chemoradiotherapy (CRT) is the standard treatment for advanced rectal cancer. Yet, the response to CRT varies from complete response to zero tumor regression.

Materials and Methods

The impact of intratumoral budding (ITB) and intratumoral CD8+ cell density on response to CRT and survival were evaluated in biopsy samples from 266 patients with advanced rectal cancer who were treated with long-course neoadjuvant CRT. The expression of epithelial-mesenchymal transition (EMT) markers was compared between patients with high and low ITB, using data from 174 patients with RNA sequencing.

Results

High ITB was observed in 62 patients (23.3%). There was no association between ITB and CD8+ cell density. The multivariable logistic regression analysis showed that high CD8+ cell density (OR, 2.69; 95% CI, 1.45-4.98; P = .002) was associated with good response to CRT, whereas high ITB (OR, 0.33; 95% CI, 0.14-0.80; P = .014) was associated with poor response. Multivariable Cox regression analysis for survival showed that high CD8+ cell density was associated with better recurrence-free survival (HR, 0.41; 95% CI, 0.24-0.72; P = .002) and overall survival (HR, 0.36; 95% CI, 0.17-0.74; P = .005), but significance values for ITB were marginal (P = .104 for recurrence-free survival and P = .163 for overall survival). The expression of EMT-related genes was not significantly different between patients with high and low ITB.

Conclusion

ITB and CD8+ cell density in biopsy samples may serve as useful biomarkers to predict therapy response in patients with rectal cancer treated with neoadjuvant CRT.

中文翻译：

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治疗前活检中的瘤内出芽和 CD8 阳性 T 细胞密度作为晚期直肠癌新辅助放化疗反应的预测因子

背景

新辅助放化疗（CRT）是晚期直肠癌的标准治疗方法。然而，对 CRT 的反应各不相同，从完全反应到肿瘤零消退。

材料和方法

在 266 名接受长程新辅助 CRT 治疗的晚期直肠癌患者的活检样本中，评估了瘤内出芽 (ITB) 和瘤内 CD8+ 细胞密度对 CRT 反应和生存的影响。使用 174 名患者的 RNA 测序数据，比较了高 ITB 患者和低 ITB 患者之间上皮-间质转化 (EMT) 标志物的表达。

结果

62 名患者 (23.3%) 观察到高 ITB。ITB 和 CD8+ 细胞密度之间没有关联。多变量逻辑回归分析显示，高 CD8+ 细胞密度（OR，2.69；95% CI，1.45-4.98；P  = .002）与 CRT 的良好反应相关，而高 ITB（OR，0.33；95% CI，0.14） -0.80；P  = .014) 与不良反应相关。生存的多变量 Cox 回归分析表明，高 CD8+ 细胞密度与更好的无复发生存（HR，0.41；95% CI，0.24-0.72；P  = 0.002）和总生存（HR，0.36；95% CI， 0.17-0.74；P  = .005），但 ITB 的显着性值很小（ 无复发生存期P = .104， 总生存期P = .163）。高、低ITB患者EMT相关基因的表达无显着差异。

结论

活检样本中的 ITB 和 CD8+ 细胞密度可作为有用的生物标志物来预测接受新辅助 CRT 治疗的直肠癌患者的治疗反应。