RNF43 p.G659fs 通过 PI3K/AKT/mTOR 信号通路和 HLA-E 上调导致 MSI-high 结直肠癌中 NK 细胞功能障碍
RNF43 p.G659fs leads to natural killer cell dysfunction in MSI-high colorectal cancer through PI3K/AKT/mTOR signaling and HLA-E up-regulation.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
肿瘤免疫微环境生物标志物用于预测局部晚期直肠癌患者新辅助放化疗后的复发
英文原题：Tumor Immune Microenvironment Biomarkers for Recurrence Prediction in Locally Advanced Rectal Cancer Patients after Neoadjuvant Chemoradiotherapy.
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Tumor Immune Microenvironment Biomarkers for Recurrence Prediction in Locally Advanced Rectal Cancer Patients after Neoadjuvant Chemoradiotherapy.
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研究概要
CD8+ T 细胞和 AI 驱动的免疫表型，连同临床因素，可以指导接受 nCRT 的 LARC 患者的个体化治疗。nCRT 后改变 TiME 的治疗策略可能有助于减少术后复发。
研究思路结论见上方概要
背景
肿瘤微环境（TME）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和TME生物标志物，识别接受新辅助放化疗（nCRT）后手术的局部晚期直肠癌（LARC）患者的预后因素。
方法
通过免疫组化染色分析CD8 + T细胞、CXCR3、CXCL10和α-平滑肌肌动蛋白（α-SMA）。我们还结合了AI驱动的数字病理学来评估空间TME。评估了这些生物标志物、临床病理参数和生存结局之间的关联。
结果
CD8 + T细胞表达、TIL（肿瘤浸润淋巴细胞）（TILs）中CXCR3表达与免疫表型相关。CD8 + T细胞、TILs中CXCR3高表达且呈炎症表型的LARC患者预后显著优于对应患者。在多变量分析中，CD8 + T细胞表达和炎症/免疫排斥表型是复发无生存期（RFS）的显著肿瘤免疫微环境（TiME）生物标志物，但不是总生存期（OS）的显著生物标志物。值得注意的是，无论病理分期如何，即使给予术后化疗，免疫荒漠表型患者预后仍较差（p < 0.001）。
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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.
论文信息
- 作者
- Hwang JE、Kim SS、Bang HJ、Kim HJ、Shim HJ、Bae WK、Chung IJ、Sun EG
- 单位
- Division of Hematology and Oncology, Department of Internal Medicine, Chonnam National University Medical School and Hwasun Hospital, Hwasun 61469, Republic of Korea.South Korea
- 期刊
- Cancers2024 Sep 30
- 原文标识
- PubMed 39409972 · DOI 10.3390/cancers16193353
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