IMMUNOREACT 8: Immune markers of local tumor spread in patients undergoing transanal excision for clinically N0 rectal cancer

IF 3.2 2区医学 Q1 SURGERY

Surgery Pub Date : 2025-02-01 DOI:10.1016/j.surg.2024.09.043

Giulia Becherucci MD , Cesare Ruffolo MD, PhD , Melania Scarpa MS, PhD , Federico Scognamiglio MS , Astghik Stepanyan MS , Isacco Maretto MD , Andromachi Kotsafti MS, PhD , Ottavia De Simoni MD , Pierluigi Pilati MD , Boris Franzato MD , Antonio Scapinello MD , Francesca Bergamo MD , Marco Massani MD , Tommaso Stecca MD , Anna Pozza MD , Ivana Cataldo MD , Stefano Brignola MD , Valerio Pellegrini MD , Matteo Fassan MD , Vincenza Guzzardo MS , Marco Scarpa MD, PhD

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引用次数: 0

Abstract

Background

Transanal excision of rectal cancer can be considered the definitive surgical treatment if the depth spread is T1 or lower, and the lesion is completely included within the resection margin. This study aims to analyze the immune microenvironment in healthy rectal mucosa as a possible predictor of tumor infiltration depth, lateral tumor spread, and recurrence of rectal cancer after transanal local excision.

Methods

This study is a subanalysis of data from the IMMUNOREACT 1 and 2 trials (NCT04915326 and NCT04917263, respectively) including all the patients who underwent transanal excision of rectal cancer. This multicentric study collected healthy mucosa surrounding the neoplasms of patients with rectal cancer. A panel of immune markers was investigated at immunohistochemistry: CD3, CD4, CD8, CD8β, Tbet, FoxP3, PD-L1, MSH6, and PMS2 and CD80. Flow cytometry determined the proportion of epithelial cells expressing CD80, CD86, CD40, HLA ABC or HLA DR and the proportion of activated CD8+ T cells, CD4+ Th1 cells, and Treg.

Results

Receiver operating characteristic curve analysis for predicting deep tumor spread showed an area under the curve of 0.70 (95% confidence interval: 0.60–0.80) for CD25+FoxP3+ cell rate and 0.74 (95% confidence interval: 0.53–0.92) for CK+CD86+ cell rate. Receiver operating characteristic curve analysis for predicting lateral tumor spread showed an area under the curve of 0.82 (95% confidence interval: 0.61–0.99) for CD8+CD38+ MFI, 0.96 (95% confidence interval: 0.85–0.99) for CD8β infiltration, and 0.97 (95% confidence interval: 0.87–0.99) for CK+HLAabc+ cell rate. Receiver operating characteristic curve analysis for predicting recurrence showed an area under the curve of 0.93 (95% confidence interval: 0.76–0.99) for CD8+CD38+ MFI and 0.94 (95% confidence interval: 0.78–0.99) for CD8+CD28+ MFI. Low CD8+CD38+ MFI and low CD8+CD28+ MFI were associated with shorter disease-free survival (P = .025 and P = .021, respectively).

Conclusion

Our study showed that the association between the high proportion of epithelial cells acting as presenting cells and deep or lateral tumor spread may be explained by the presence of a greater tumor load at the site. Moreover, it showed that weak activation of CD8+ T cells within the rectal mucosa is associated with lateral tumor spread and eventually a higher recurrence rate. The mucosal level of CD8β infiltration detected at immunohistochemistry might be tested as a marker of lateral tumor spread and potentially translated into clinical practice.

查看原文本刊更多论文

IMMUNOREACT 8：经肛门切除术治疗临床 N0 直肠癌患者局部肿瘤扩散的免疫标记物。

背景：如果直肠癌的扩散深度为T1或更低，且病灶完全包括在切除边缘内，则经肛门切除直肠癌可被视为最终的手术治疗方法。本研究旨在分析健康直肠粘膜的免疫微环境，以此作为经肛局部切除术后肿瘤浸润深度、肿瘤侧向扩散和直肠癌复发的可能预测因素：本研究是对 IMMUNOREACT 1 和 2 试验（分别为 NCT04915326 和 NCT04917263）数据的子分析，包括所有接受经肛门直肠癌切除术的患者。这项多中心研究收集了直肠癌患者肿瘤周围的健康粘膜。通过免疫组化对一系列免疫标记物进行了研究：CD3、CD4、CD8、CD8β、Tbet、FoxP3、PD-L1、MSH6、PMS2 和 CD80。流式细胞术测定了表达 CD80、CD86、CD40、HLA ABC 或 HLA DR 的上皮细胞比例，以及活化的 CD8+ T 细胞、CD4+ Th1 细胞和 Treg 的比例：预测肿瘤深部扩散的接收者操作特征曲线分析显示，CD25+FoxP3+细胞率的曲线下面积为0.70（95%置信区间：0.60-0.80），CK+CD86+细胞率的曲线下面积为0.74（95%置信区间：0.53-0.92）。预测肿瘤横向扩散的接收者操作特征曲线分析显示，CD8+CD38+ MFI 的曲线下面积为 0.82（95% 置信区间：0.61-0.99），CD8β浸润的曲线下面积为 0.96（95% 置信区间：0.85-0.99），CK+HLAabc+ 细胞率的曲线下面积为 0.97（95% 置信区间：0.87-0.99）。预测复发的接收者操作特征曲线分析显示，CD8+CD38+ MFI 的曲线下面积为 0.93（95% 置信区间：0.76-0.99），CD8+CD28+ MFI 的曲线下面积为 0.94（95% 置信区间：0.78-0.99）。低 CD8+CD38+ MFI 和低 CD8+CD28+ MFI 与较短的无病生存期相关（分别为 P = .025 和 P = .021）：我们的研究表明，作为呈现细胞的上皮细胞比例高与肿瘤向深部或侧部扩散之间的关联可能是由于该部位存在较大的肿瘤负荷。此外，研究还表明，直肠粘膜内 CD8+ T 细胞的弱激活与肿瘤的侧向扩散以及最终的高复发率有关。免疫组化检测到的 CD8β 浸润的粘膜水平可作为肿瘤侧向扩散的标志物进行检测，并有可能应用于临床实践。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Surgery 医学-外科

CiteScore

5.40

自引率

5.30%

发文量

687

审稿时长

64 days

期刊介绍： For 66 years, Surgery has published practical, authoritative information about procedures, clinical advances, and major trends shaping general surgery. Each issue features original scientific contributions and clinical reports. Peer-reviewed articles cover topics in oncology, trauma, gastrointestinal, vascular, and transplantation surgery. The journal also publishes papers from the meetings of its sponsoring societies, the Society of University Surgeons, the Central Surgical Association, and the American Association of Endocrine Surgeons.