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    CD8+/FOXP3+比值预测乳腺癌新辅助治疗疗效及预后的意义

    Study on the Significance of Intratumoral CD8+/FOXP3+ Ratio in Predicting Outcomes of Neoadjuvant Therapy in Breast Cancer

      摘要
    • 摘要:
      目的 探索CD8+与FOXP3+ T细胞在乳腺肿瘤中浸润水平的比值和乳腺癌新辅助治疗（neoadjuvant treatment，NAT）疗效及预后关系，及其在乳腺癌NAT前后的动态变化规律。
      方法 收集2014年1月至2018年11月广州医科大学附属肿瘤医院乳腺癌NAT前后配对标本104例，采用多重免疫荧光组织化学法（multiplex immunohistochemistry，mIHC）对治疗前和治疗后标本进行染色，免疫细胞亚群采用基于人工智能（artificial intelligence，AI）的方法进行量化；SPSS 25.0软件分析CD8+/FOXP3+比值与病理完全缓解（pathologic complete response，pCR）、无病生存期（disease-free-survival，DFS）、总生存期（overall survival，OS）的预测关系，及其在NAT前后的动态变化。
      结果 受试者工作特征（receiver operating characteristic，ROC）分析结果显示总区域、间质区域和肿瘤内区域的CD8+/FOXP3+比值对pCR曲线下面积（area under the curve，AUC）=0.679、0.657、0.664、DFS（AUC=0.633、0.617、0.619）和OS（AUC=0.682、0.704、0.691）均有较好预测价值。生存分析结果同样显示CD8+/FOXP3+比值高的患者具有更长的DFS（P=0.002）和OS（P=0.002）。动态分析显示，non-pCR人群中总区域、间质区域CD8+/FOXP3+比值在NAT后呈升高趋势。
      结论 CD8+/FOXP3+比值对乳腺癌NAT疗效及预后具有一定的预测价值。NAT可促进乳腺癌患者总区域和间质区域CD8+/FOXP3+免疫浸润水平的比值变化。

       

      Abstract:
      Objective The role of this research is to investigate the relationship between the ratio of CD8+/FOXP3+ tumor-infiltrating level and the neoadjuvant therapy (NAT) response and prognosis in breast cancer, and to observe the dynamic change before and after NAT.
      Methods A total of 104 cases of breast cancer between pre- and post-NAT were collected from January 2014 to November 2018 in Affiliated Cancer Hospital & Institute of Guangzhou Medical University; 104 paired pre- and post-neoadjuvant biopsieswere stained using fluorescent multiplex immunohistochemistry (mIHC); Immune cell subsets were quantified using artificial intelligence (AI)-based methods. SPSS 25.0 was used to detect the predictive value of the ratio of tumor-infiltrating CD8+/FOXP3+ to pathological complete response (pCR), disease free survival (DFS), overall survival (OS), and the dynamic change of the ratio of tumor-infiltrating CD8+/FOXP3+ between pre- and post-NAT.
      Results Receiver operating characteristic(ROC)analysis indicted that CD8+/FOXP3+ ratio in the Total region, Stromal region and Intratumoral region were statistically significant and independent predictors of pCRarea under the curve(AUC)=0.679, 0.657, 0.664, DFS(AUC=0.633, 0.617, 0.619)and OS (AUC=0.682, 0.704, 0.691), respectively. Meanwhile, survival analysis also showed that patients with a high CD8+/FOXP3+ ratio had longer DFS(P=0.002)and OS(P=0.002). Dynamic analysis suggested that the Total region, Stromal region CD8+/FOXP3+ ratio increased after NAT in the non-pCR people.
      Conclusions The ratio of tumor-infiltrating CD8+/FOXP3+ has a good predictive value for the NAT response and prognosis in breast cancer. Meanwhile, NAT could promote the Total, Stromal tumor-infiltrating level of CD8+/FOXP3+ ratio in breast cancer.

       

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