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未经治疗的可切除胃癌患者基于活检的免疫评分

A biopsy-based Immunoscore in patients with treatment-naïve resectable gastric cancer.

作者信息

Soeratram Tanya T D, Beentjes Isis, Egthuijsen Jacqueline M P, Mookhoek Aart, Lange Marilyne M, Meershoek-Klein Kranenbarg Elma, Hartgrink Henk H, van de Velde Cornelis J H, Ylstra Bauke, van Laarhoven Hanneke W M, van Grieken Nicole C T

机构信息

Department of Pathology, Amsterdam UMC location VUmc, Amsterdam, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.

Cancer Center Amsterdam, Cancer Biology and Immunology, Amsterdam, The Netherlands.

出版信息

Ther Adv Med Oncol. 2024 Oct 21;16:17588359241287747. doi: 10.1177/17588359241287747. eCollection 2024.

Abstract

BACKGROUND

The prognostic significance of T-cell densities in gastric cancer (GC) was previously demonstrated in surgical resection specimens. For prognosis or response prediction, it is preferable to identify biomarkers in pre-treatment biopsies; yet, its representativeness of the tumor immune microenvironment is unclear.

OBJECTIVES

This study aimed to evaluate the concordance and prognostic value of T-cell densities in paired biopsies and resections.

METHODS

Paired diagnostic biopsies and surgical resections were available for 131 patients with resectable GC who were treated with surgery alone in the D1/D2 trial. T-cell markers such as CD3, CD45RO, CD8, FOXP3, and Granzyme B were assessed by immunohistochemistry and digitally quantified. Tumors were categorized into high and low subgroups for each marker. The concordance between biopsies and resections was determined for each marker with Cohen's κ. To determine the prognostic value of T cells in biopsies, Cox regression was performed.

RESULTS

The concordance of T-cell high and low tumors was moderate for CD8 (κ = 0.58) and weak for other markers (κ < 0.3). CD8 and FOXP3 densities in biopsies were significantly associated with cancer-specific survival. Multivariable analysis showed that an Immunoscore incorporating CD8 and FOXP3 served as an independent prognostic marker (low vs high: hazard ratio 3.40, 95% confidence interval: 1.27-9.10;  = 0.015).

CONCLUSION

Although the concordance in T-cell densities between biopsy and resection specimens is modest, a biopsy-based Immunoscore identified distinct biological subgroups with prognostic potential. To fully evaluate the prognostic performance of this biopsy Immunoscore, additional studies are warranted.

摘要

背景

先前在手术切除标本中已证实胃癌(GC)中T细胞密度的预后意义。对于预后或反应预测而言,在治疗前活检中识别生物标志物更为可取;然而,其对肿瘤免疫微环境的代表性尚不清楚。

目的

本研究旨在评估配对活检和切除标本中T细胞密度的一致性及预后价值。

方法

在D1/D2试验中,131例接受单纯手术治疗的可切除GC患者有配对的诊断性活检和手术切除标本。通过免疫组织化学对T细胞标志物如CD3、CD45RO、CD8、FOXP3和颗粒酶B进行评估并数字化定量。每种标志物的肿瘤被分为高分组和低分组。使用Cohen's κ确定每种标志物活检和切除标本之间的一致性。为了确定活检中T细胞的预后价值,进行Cox回归分析。

结果

CD8的T细胞高肿瘤和低肿瘤的一致性为中等(κ = 0.58),其他标志物的一致性较弱(κ < 0.3)。活检中CD8和FOXP3密度与癌症特异性生存显著相关。多变量分析显示,纳入CD8和FOXP3的免疫评分作为独立的预后标志物(低分组与高分组:风险比3.40,95%置信区间:1.27 - 9.10;P = 0.015)。

结论

尽管活检和切除标本之间T细胞密度的一致性一般,但基于活检的免疫评分可识别出具有预后潜力的不同生物学亚组。为了全面评估这种活检免疫评分的预后性能,有必要进行更多研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c18c/11497501/4b9ff2a34859/10.1177_17588359241287747-img2.jpg

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