The tumor immune microenvironment of SCLC is not associated with its molecular subtypes

IF 7.6 1区医学 Q1 ONCOLOGY

European Journal of Cancer Pub Date : 2024-10-15 DOI:10.1016/j.ejca.2024.115067

Yoan Velut , Basilia Arqué , Marie Wislez , Hélène Blons , Barbara Burroni , Mathilde Prieto , Siméon Beau , Ludovic Fournel , Gary Birsen , Isabelle Cremer , Marco Alifano , Diane Damotte , Audrey Mansuet-Lupo

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引用次数: 0

Abstract

Introduction

Small-cell lung carcinoma (SCLC) is a high-grade neuroendocrine carcinoma of poor prognosis. Although immune checkpoint blockers have shown promising results in advanced SCLC, the tumor immune microenvironment (TME) remains poorly understood, with no validated prognostic or predictive biomarkers of efficacy.

Methods

This retrospective study included surgically samples from 48 SCLC patients between 2009 and 2018. We assessed the TME using two quantitative 7-plex immunofluorescence panels focusing on T and B cells, and compared it to NSCLC (N = 10). Molecular subtypes were determined by assessing the expression of ASCL1, NEUROD1 and YAP1 using immunohistochemistry.

Results

Immune-hot SCLC were defined as those exhibiting the highest immune cell and immune-related marker densities. They were associated with longer overall survival, significantly more frequently detected at early stages, and exhibited high PD-L1 expression in immune cells, but were not associated with molecular subtypes. Compared to NSCLC, SCLC had significantly lower densities of CD20 + cells and higher density of PD1 + cells, with no significant differences in CD4 + , CD8 + and plasma cell densities. In univariate analysis, the highest OS was significantly associated with early stage (p < 0.001), low expression of NEUROD1 (p = 0.047), high PD1 + cell density (p < 0.001) and high PD-L1 immune cell expression (p = 0.04). Only stage and PD1 + cell density emerged as independent prognostic markers.

Conclusion

SCLC TME is highly heterogeneous. Immune-hot tumors were associated with OS but not with molecular classification. PD1 expression and PD-L1 expression by immune cells may thus serve as a prognostic marker.

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SCLC 的肿瘤免疫微环境与其分子亚型无关

导言小细胞肺癌（SCLC）是一种预后不良的高级别神经内分泌癌。尽管免疫检查点阻断剂在晚期SCLC中显示出了良好的效果，但人们对肿瘤免疫微环境（TME）的了解仍然很少，没有有效的预后或疗效预测生物标志物。方法这项回顾性研究纳入了2009年至2018年间48例SCLC患者的手术样本。我们使用两种以T细胞和B细胞为重点的定量7倍免疫荧光面板评估了TME，并将其与NSCLC（N = 10）进行了比较。结果免疫热SCLC被定义为免疫细胞和免疫相关标记物密度最高的SCLC。它们与较长的总生存期相关，更常在早期阶段被发现，并在免疫细胞中表现出较高的PD-L1表达，但与分子亚型无关。与NSCLC相比，SCLC的CD20 +细胞密度明显较低，而PD1 +细胞密度较高，CD4 +、CD8 +和浆细胞密度无明显差异。在单变量分析中，最高OS与早期分期（p < 0.001）、NEUROD1低表达（p = 0.047）、PD1 +细胞高密度（p < 0.001）和PD-L1免疫细胞高表达（p = 0.04）明显相关。只有分期和 PD1 + 细胞密度成为独立的预后标志物。免疫热肿瘤与OS相关，但与分子分类无关。因此，免疫细胞的PD1表达和PD-L1表达可作为预后标志物。

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

European Journal of Cancer 医学-肿瘤学

CiteScore

11.50

自引率

4.80%

发文量

953

审稿时长

23 days

期刊介绍： The European Journal of Cancer (EJC) serves as a comprehensive platform integrating preclinical, digital, translational, and clinical research across the spectrum of cancer. From epidemiology, carcinogenesis, and biology to groundbreaking innovations in cancer treatment and patient care, the journal covers a wide array of topics. We publish original research, reviews, previews, editorial comments, and correspondence, fostering dialogue and advancement in the fight against cancer. Join us in our mission to drive progress and improve outcomes in cancer research and patient care.