共刺激分子CD70的表达对小细胞肺癌具有预后价值。

Expression of costimulatory molecule CD70 is prognostic in small cell lung cancer.

作者信息

Dora David, Megyesfalvi Zsolt, Vörös Imre, Paál Ágnes, Takacs Peter, Dobos Daniela, Lőrincz Bence, Bokhari Syeda Mahak Zahra, Aloss Kenan, Pallag Gergely, Rivard Christopher, Yu Hui, Hirsch Fred R, Görbe Anikó, Varga Zoltán V, Lohinai Zoltan, Dome Balazs

机构信息

Department of Anatomy, Histology, and Embryology, Faculty of Medicine, Semmelweis University, Budapest, Hungary.

Department of Tumor Biology, National Koranyi Institute of Pulmonology, Budapest, Hungary.

出版信息

Cancer Immunol Immunother. 2025 Apr 9;74(5):165. doi: 10.1007/s00262-025-04006-2.

DOI:10.1007/s00262-025-04006-2

PMID:40205178

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11981989/

Abstract

INTRODUCTION

Small cell lung cancer (SCLC) is a highly aggressive malignancy with poor survival outcomes. The CD70-CD27 axis has been implicated in immune regulation and tumor progression across cancers, but its role in SCLC has not yet been elucidated. This research explores the expression patterns and prognostic significance of CD70 and CD27 in early-stage SCLC.

METHODS

In this retrospective study, we analyzed 190 surgically resected SCLC tumor samples using immunohistochemistry (IHC) for CD70 and CD27 expression and RNAscope for CD70 RNA detection. Immune infiltration was assessed using CD45, CD8, and CD20 staining. Quantification of RNAscope signals was performed using QPath software. Kaplan-Meier survival analysis and multivariate Cox regression were used to assess the prognostic impact of CD70, CD27, and immune cell infiltrates on overall survival (OS).

RESULTS

CD70 was expressed in 46% of tumors, primarily within tumor nests, with lower expression in stromal areas. High CD70 expression correlated with significantly decreased OS (p = 0.0078, HR: 1.795) without any correlation with CD45 + , CD8 + or CD20 + immune cell infiltrates. CD27 expression was mainly confined to the stroma, and it did not show a significant association with OS (p = 0.582). Importantly, high CD27 expression was linked to reduced CD45 + and CD8 + cell densities in the stroma. Both CD70 and CD27 were expressed on CD68 + macrophages, CD27 was expressed on CAFs, and both molecules exhibited a partial coexpression with CD3. Furthermore, patients with high CD20 + B-cell densities or the presence of tertiary lymphoid structures (TLS) had significantly improved OS (p = 0.0017, HR: 0.491), suggesting the importance of B-cell-related immune responses in SCLC prognosis.

CONCLUSION

CD70, B-cell density and the presence of TLSs, but not CD27, emerged as a significant prognostic biomarker for OS in surgically treated SCLC, suggesting its potential as a therapeutic target.

摘要

引言

小细胞肺癌（SCLC）是一种侵袭性很强的恶性肿瘤，生存预后较差。CD70 - CD27轴在多种癌症的免疫调节和肿瘤进展中发挥作用，但其在SCLC中的作用尚未阐明。本研究探讨CD70和CD27在早期SCLC中的表达模式及预后意义。

方法

在这项回顾性研究中，我们使用免疫组织化学（IHC）检测190例手术切除的SCLC肿瘤样本中CD70和CD27的表达，并使用RNAscope检测CD70 RNA。通过CD45、CD8和CD20染色评估免疫浸润情况。使用QPath软件对RNAscope信号进行定量分析。采用Kaplan - Meier生存分析和多变量Cox回归评估CD70、CD27和免疫细胞浸润对总生存期（OS）的预后影响。

结果

46%的肿瘤表达CD70，主要在肿瘤巢内，基质区域表达较低。高CD70表达与OS显著降低相关（p = 0.0078，HR：1.795），与CD45 +、CD8 +或CD20 +免疫细胞浸润无相关性。CD27表达主要局限于基质，与OS无显著相关性（p = 0.582）。重要的是，高CD27表达与基质中CD45 +和CD8 +细胞密度降低有关。CD70和CD27均在CD68 +巨噬细胞上表达，CD27在癌相关成纤维细胞（CAF）上表达，且这两种分子均与CD3有部分共表达。此外，CD20 + B细胞密度高或存在三级淋巴结构（TLS）的患者OS显著改善（p = 0.0017，HR：0.491），表明B细胞相关免疫反应在SCLC预后中的重要性。