三级淋巴结构对非小细胞肺癌患者新辅助治疗后病理反应及预后的影响  

Effect of tertiary lymphoid structures on pathological response and prognosis after neoadjuvant therapy for non-small cell lung cancer

作　　者：薛孟丽 耿华[2] 李世雄 丁运 徐美林[1,2] Mengli Xue;Hua Geng;Shixiong Li;Yun Ding;Meilin Xu(Clinical College of Chest,Tianjin Medical University,Tianjin 300041,China;Department of Pathology,Tianjin Chest Hospital,Tianjin 300222,China;Department of Thoracic Surgery,Tianjin Chest Hospital,Tianjin 300222,China)

机构地区：[1]天津医科大学胸科临床学院,天津市300041 [2]天津市胸科医院病理科 [3]天津市胸科医院胸外科

出　　处：《中国肿瘤临床》2024年第9期454-460,共7页Chinese Journal of Clinical Oncology

基　　金：北京医学奖励基金会项目(编号:YXJT-2021-646-479)资助。

摘　　要：目的:研究三级淋巴结构(tertiary lymphoid structures,TLS)对接受新辅助治疗非小细胞肺癌(non-small cell lung cancer,NSCLC)患者的病理反应及预后的影响。方法:回顾性收集2019年1月至2023年12月于天津市胸科医院接受新辅助治疗后行手术的NSCLC患者132例,分为新辅助化疗(neoadjuvant chemotherapy,NC)组40例和新辅助化疗联合免疫治疗(neoadjuvant chemotherapy combined with immunotherapy,NCI)组92例。通过H&E染色评估切片中残余肿瘤细胞(residual viable tumor,RVT)百分比和肿瘤浸润淋巴细胞(tumor infiltrating lymphocyte,TIL),采用H&E染色和免疫组织化学染色方法评估TLS数量和成熟度,分析两组中TLS数量和成熟度的差异以及对患者病理反应和预后的影响。结果:NCI组中TIL浸润水平、TLS的总数量、成熟数量以及病理完全缓解(pathologic complete response,pCR)率、主要病理缓解(major pathologic response,MPR)率均明显高于NC组(均P<0.001)。多因素Logistic分析结果显示,成熟TLS数量和TIL浸润是NCI组患者病理反应的影响因素(P<0.05)。多元线性回归分析结果表明,在NC组中TIL低浸润是高RVT的危险因素;同时在NCI组中,成熟TLS数量低、TIL低浸润和治疗前N分期是高RVT的独立危险因素(均P<0.05)。多因素Cox回归分析结果显示成熟TLS数量(P=0.001)和TIL(P=0.009)是NCI组患者无病生存期(disease-free survival,DFS)的独立预测因子,并且生存分析显示NCI组中TLS高成熟和TIL高浸润患者的DFS显著优于低成熟和低浸润者(均P<0.001)。结论:TLS低成熟度和TIL低浸润与NSCLC患者不良的病理反应和较短的DFS有关,TLS成熟度和TIL可以作为接受NCI患者的病理反应和预后的预测指标。Objective:To study the effect of tertiary lymphoid structures(TLS)on the pathological response and prognosis of patients with non-small cell lung cancer(NSCLC)receiving neoadjuvant therapy.Methods:We retrospectively collected the data of 132 patients with NSCLC who underwent neoadjuvant therapy and surgery at Tianjin Chest Hospital between January 2019 and December 2023,including 40 in the neoadjuvant chemotherapy(NC)group and 92 in the NC plus immunotherapy(NCI)group.The percentage of residual viable tumor(RVT)and tumor infiltrating lymphocyte(TIL)counts were evaluated by hematoxylin and eosin(H&E)staining,while TLS number and maturity were assessed by H&E and immunohistochemical staining.The differences in TLS number and maturity and effects on patient pathological response and prognosis were compared between groups.Results:TIL count,total TLS number,pathological complete response and major pathological response rates were significantly higher in the NCI versus NC group(P<0.001).Moreover,a multivariate Logistic analysis showed that TLS number and maturity and TIL count affected pathological response in the NCI group(P<0.05).A multiple linear regression analysis indicated that a low TIL count was a risk factor for a high RVT in the NC group,while a low number of mature TLS,low TIL count,and N stage were independent risk factors for a high RVT in the NCI group(all P<0.05).In the NCI group,a multivariate Cox regression analysis showed that a low number of mature TLS(P=0.001)and low TIL count(P=0.009)were independent predictors of disease-free survival(DFS),while a survival analysis showed that patients in the NCI group with high(vs.low)numbers of mature TLS and a high(vs.low)TIL count had significantly longer DFS(all P<0.001).Conclusions:A low number of mature TLS and low TIL count were associated with an adverse pathological response and short DFS in patients with NSCLC.Thus,TLS maturity and TIL count can predict the pathological response and prognosis of patients with NSCLC treated with NCI.

关 键 词：三级淋巴结构 肿瘤浸润淋巴细胞 非小细胞癌 新辅助治疗 

分 类 号：R734.2[医药卫生—肿瘤]