新辅助化疗后局部晚期直肠癌患者三级淋巴结构参数与预后的相关性分析：一项回顾性研究

Correlation analysis of tertiary lymphoid structure parameters with the prognosis of patients with locally advanced rectal cancer after neoadjuvant chemotherapy: a retrospective study.

作者信息

Jiang Yingjian, Zhang Chuang, Hou Yifei, Zhao Bin, Cui Binbin

机构信息

Department of Colorectal Surgery, Harbin Medical University Cancer Hospital, No.150 Haping Road, Harbin City, 150081, Heilongjiang Province, China.

School of Nursing, Harbin Medical University, Harbin, 150081, Heilongjiang Province, China.

出版信息

World J Surg Oncol. 2025 Apr 9;23(1):131. doi: 10.1186/s12957-025-03796-0.

DOI:10.1186/s12957-025-03796-0

PMID:40205382

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11980294/

Abstract

BACKGROUND

The tertiary lymphoid structures (TLSs) are positively correlated with the prognosis of many solid tumors, including colorectal cancer. However, their prognostic significance in patients with locally advanced rectal cancer (LARC) after neoadjuvant chemotherapy remains unclear. This study aimed to explore the correlation between TLS parameters and the prognosis of LARC patients receiving neoadjuvant chemotherapy.

METHODS

This retrospective study included patients with LARC treated at the Harbin Medical University Cancer Hospital from 2012 to 2021. The quantity, area, and density of TLSs in the tumor, normal, and total tissues from surgical specimens were determined. Overall survival (OS) was calculated from surgery to death from any cause. The correlation between TLS parameters and prognosis was assessed using Kaplan-Meier survival analysis and Cox regression analysis. Multiplex immunofluorescence (mIF) staining was used to analyze TLS maturity and immune composition.

RESULTS

This study included 114 patients, of whom 46.5% were over 60 years old, and 70.2% were male. TLS parameters in tumor region were smaller than those in normal and total regions (P < 0.001). A larger TLS area and higher density in the total region (HR = 0.371, P = 0.023 for area; HR = 0.250, P = 0.005 for density) were significantly associated with better OS. Moreover, a higher total-region TLS density was correlated with low carcinoembryonic antigen (CEA) levels (P = 0.028), positive responses to neoadjuvant therapy (P < 0.001), and tumor regression (P < 0.001). Subgroup analysis revealed that combining total-region TLS density with clinicopathologic features such as sex, age, cTNM stage, CEA levels, and extramural vascular invasion further stratified prognosis. Additionally, mIF analysis showed that a high TLS density was associated with a higher TLS maturity (P = 0.014); mature TLSs exhibited greater infiltration of CD20⁺ B cells and CD21⁺ follicular dendritic cells compared to non-mature TLSs.

CONCLUSIONS

TLS parameters, particularly TLS density, are promising prognostic biomarkers for LARC patients undergoing neoadjuvant chemotherapy.

TRIAL REGISTRATION

not applicable.

摘要

背景

三级淋巴结构（TLSs）与包括结直肠癌在内的许多实体瘤的预后呈正相关。然而，它们在新辅助化疗后局部晚期直肠癌（LARC）患者中的预后意义仍不清楚。本研究旨在探讨TLS参数与接受新辅助化疗的LARC患者预后之间的相关性。

方法

这项回顾性研究纳入了2012年至2021年在哈尔滨医科大学附属肿瘤医院接受治疗的LARC患者。测定手术标本中肿瘤组织、正常组织和全组织中TLSs的数量、面积和密度。总生存期（OS）从手术开始计算至因任何原因死亡。使用Kaplan-Meier生存分析和Cox回归分析评估TLS参数与预后之间的相关性。采用多重免疫荧光（mIF）染色分析TLS成熟度和免疫组成。

结果

本研究纳入114例患者，其中46.5%年龄超过60岁，70.2%为男性。肿瘤区域的TLS参数小于正常区域和全组织区域（P < 0.001）。全组织区域中更大的TLS面积和更高的密度（面积：HR = 0.371，P = 0.023；密度：HR = 0.250，P = 0.005）与更好的OS显著相关。此外，全组织区域更高的TLS密度与低癌胚抗原（CEA）水平（P = 0.028）、对新辅助治疗的阳性反应（P < 0.001）和肿瘤退缩（P < 0.001）相关。亚组分析显示，将全组织区域TLS密度与性别、年龄、cTNM分期、CEA水平和壁外血管侵犯等临床病理特征相结合可进一步分层预后。此外，mIF分析显示，高TLS密度与更高的TLS成熟度相关（P = 0.014）；与未成熟TLS相比，成熟TLS表现出更多的CD20⁺ B细胞和CD21⁺滤泡树突状细胞浸润。