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

作　　者：钟艳华 张乐瑶 黄嘉 何伟星 喻晓丹 梁红玲 ZHONG Yan-hua;ZHANG Le-yao;HUANG Jia;HE Wei-xing;YU Xiao-dan;LIANG Hong-ling(Department of Breast Surgery,Affiliated Cancer Hospital&Institute of Guangzhou Medical University,Guangzhou 510095,China;Guangzhou Medical University,Guangzhou 510006,China;Breast and Thyroid Department of Guangzhou Women and Childrens Medical Center Liuzhou Hospital,Guangxi Liuzhou 545005,China)

机构地区：[1]广州医科大学附属肿瘤医院乳腺外科,广州510095 [2]广州医科大学,广州510006 [3]广州市妇女儿童医疗中心柳州医院乳腺甲状腺科,广西柳州545005

出　　处：《循证医学》2023年第6期378-386,共9页The Journal of Evidence-Based Medicine

基　　金：广州市科学技术局(202102080096);广州市科学技术局一般引导项目(201904010331);广州市科技计划项目(2023A03J043);广东省科学技术厅省自然科学基金(2022A1515012376);广东省教育厅(2021KTSCX091);广东省教育厅普通高校特色创新项目(2020KTSCX105)。

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。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 MedicalUniversity;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 todetect 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 independentpredictors of pCR[area 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,Stromalregion 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 couldpromote the Total,Stromal tumor⁃infiltrating level of CD8+/FOXP3+ ratio in breast cancer.

关 键 词：乳腺癌 新辅助治疗 肿瘤浸润免疫细胞 CD8 FOXP3 

分 类 号：R737.9[医药卫生—肿瘤]