文章：

新辅助放化疗后局部晚期直肠癌患者肿瘤免疫微环境生物标志物用于复发预测

Tumor Immune Microenvironment Biomarkers for Recurrence Prediction in Locally Advanced Rectal Cancer Patients after Neoadjuvant Chemoradiotherapy

原文发布日期：30 September 2024

DOI: 10.3390/cancers16193353

类型: Article

开放获取: 是

英文摘要：

Background/Objectives: The tumor microenvironment (TME) has emerged as a significant prognostic factor. This study aimed to identify prognostic factors by combining clinicopathologic parameters and the TME biomarkers in patients who underwent surgery following neoadjuvant chemoradiotherapy (nCRT) for locally advanced rectal cancer (LARC). Methods: CD8+T cells, CXCR3, CXCL10, and α-smooth muscle actin (α-SMA) were analyzed via immunohistochemical staining. We also incorporated AI-powered digital pathology to assess the spatial TME. The associations between these biomarkers, clinicopathologic parameters, and survival outcomes were evaluated. Results: CD8+T cell expression, CXCR3 expression in tumor-infiltrating lymphocytes (TILs), and immune phenotypes were correlated. LARC patients with a high expression of CD8+T cells, CXCR3 in TILs, and an inflamed phenotype had a significantly better prognosis than their counterparts did. In the multivariate analysis, the expression of CD8+T cells and the inflamed/immune-excluded phenotype were significant tumor immune microenvironment (TiME) biomarkers for recurrence-free survival (RFS) but not for overall survival (OS). Notably, patients with the immune-desert phenotype had a poor prognosis regardless of pathologic stage, even if postoperative chemotherapy was administered (p< 0.001). Conclusions: CD8+T cells and AI-powered immune phenotypes, alongside clinical factors, can guide personalized treatment in LARC patients receiving nCRT. A therapeutic strategy to modify the TiME after nCRT could help reduce recurrence after surgery.

摘要翻译： 

背景/目的：肿瘤微环境已成为重要的预后因素。本研究旨在通过结合临床病理参数与肿瘤微环境生物标志物，确定接受新辅助放化疗后手术治疗的局部晚期直肠癌患者的预后因素。方法：通过免疫组织化学染色分析CD8+T细胞、CXCR3、CXCL10及α-平滑肌肌动蛋白表达水平，并采用人工智能数字病理技术评估空间肿瘤微环境特征。评估这些生物标志物、临床病理参数与生存结局之间的关联性。结果：CD8+T细胞表达水平、肿瘤浸润淋巴细胞中CXCR3表达与免疫表型存在相关性。CD8+T细胞高表达、肿瘤浸润淋巴细胞CXCR3高表达及炎症表型的局部晚期直肠癌患者预后显著优于对照组。多变量分析显示，CD8+T细胞表达水平及炎症型/免疫排斥型表型是肿瘤免疫微环境中无复发生存期的显著预测标志物，但对总生存期无显著预测价值。值得注意的是，无论病理分期如何，即使接受术后化疗，免疫荒漠型表型患者仍预后不良（p<0.001）。结论：CD8+T细胞与人工智能判读的免疫表型结合临床因素，可指导接受新辅助放化疗的局部晚期直肠癌患者个体化治疗。新辅助放化疗后调控肿瘤免疫微环境的治疗策略可能有助于降低术后复发风险。

原文链接：

Tumor Immune Microenvironment Biomarkers for Recurrence Prediction in Locally Advanced Rectal Cancer Patients after Neoadjuvant Chemoradiotherapy