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CD4⁺、CD8⁺ 和 FOXP3⁺ TIL(肿瘤浸润淋巴细胞)预测浸润性乳腺癌新辅助化疗反应

英文原题:Response to Neoadjuvant Chemotherapy in Invasive Breast Cancer Predicted by CD4+, CD8+, and FOXP3+ Tumor-Infiltrating Lymphocytes.

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Response to Neoadjuvant Chemotherapy in Invasive Breast Cancer Predicted by CD4+, CD8+, and FOXP3+ Tumor-Infiltrating Lymphocytes.

PubMed 2024/05/01(内容时间) Asian Pac J Cancer Prev

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研究概要

本研究表明,CD4⁺、CD8⁺ 和 FOXP3⁺ TIL 作为预测性生物标志物具有良好潜力。

中文摘要

浸润性乳腺癌(IBC)患者对新辅助化疗(NC)的反应必须进行监测,且需要相应生物标志物。NC 可激活肿瘤微环境中的抗肿瘤免疫反应,其中涉及TIL(肿瘤浸润淋巴细胞)。CD4+、CD8+ 和 FOXP3+ TIL 被认为具有较大预测潜力。本研究旨在探索可作为 NC 病理反应预测生物标志物的 TIL 成分。

根据 CD4+、CD8+ 和 FOXP3+ TIL 表达与 Miller-Payne(MP)分级系统的关系,分析 40 例样本。还评估年龄、肿瘤分级、PR、ER、Ki-67 和 HER2。通过免疫组织化学染色分析 CD4+、CD8+ 和 FOXP3+ TIL 表达,其余数据取自档案记录。采用单变量和多变量分析。

单变量分析显示,CD4+ TIL 与 MP 分级显著相关(p<0.001),CD8+ 与 MP 分级相关(p=0.004),FOXP3 与 MP 分级相关(p<0.001)。将三种生物标志物同时纳入一个模型,预测效果不佳。因此,研究人员进行了探索性分析,测试了由三种现有标志物中任取两种组合的多个替代模型。结果显示,模型 2(CD4+CD8+)中的 CD4+ TIL,以及模型 4(CD8+FOXP3+)中的 FOXP3+ TIL,其系数具有显著性;此外,模型 4 中所有阈值系数均显著。

本研究显示,CD4+、CD8+ 和 FOXP3+ TIL 均具有作为预测生物标志物的潜力。其中,FOXP3+ 在 IBC 患者病理反应预测模型中占主导地位。

展开英文摘要原文

Response to neoadjuvant chemotherapy (NC) in individuals with invasive breast cancer (IBC) must be monitored, and biomarkers are needed. NC can activate an anti-tumour immune response in its microenvironment, known as Tumor-infiltrating Lymphocytes (TIL). TIL components believed to have great potential as predictors are CD4+, CD8+, and FOXP3+ TIL. This study aims to explore TIL components that can potentially be predictive biomarkers of NC pathological responses.

A sample size of 40 were analyzed based on the relationship between CD4+, CD8+, and FOXP3+ TIL expression with the Miller-Payne (MP) grading system. Age, tumour grade, PR, ER, Ki-67, and HER2 were also evaluated. CD4+, CD8+, and FOXP3+ TIL expressions were analayzed by IHC staining, while other data were collected from archives. Data was analyzed using univariate and multivariate analysis.

Univariate analysis showed a significant relationship between CD4+ TIL and MP (p<0.001), CD8+ and MP (p=0.004), and FOXP3 with MP (p<0.001). The simultaneous integration of the three biomarkers in one model was not good enough to be a predictive model. Therefore, an exploratory analysis was conducted by testing several alternative models that combined two of the three existing biomarkers. It turned out that CD4+ TIL in model 2 (CD4+CD8+) and FOXP3+ TIL in model 4 (CD8+FOXP3+) showed significant coefficient values. Moreover, all of the threshold coefficients in model 4 are significant.

This study shows that CD4+, CD8+, and FOXP3+ TIL have promising potential as predictive biomarkers. In particular, FOXP3+ is dominant in predictive models of pathological response in patients with IBC.

论文信息

作者
Rustamadji P、Wiyarta E、Pramono M、Maulanisa SC
单位
Department of Anatomic Pathology, Faculty of Medicine Universitas Indonesia-Dr. Cipto Mangunkusumo National Hospital, Jakarta, Indonesia.Indonesia
期刊
Asian Pacific journal of cancer prevention : APJCP2024 May 1
原文标识
PubMed 38809632 · DOI 10.31557/APJCP.2024.25.5.1607