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喉癌中血管生成、程序性死亡配体 1(PD-L1)与免疫微环境的关联

英文原题:Angiogenesis, programmed death ligand 1 (PD-L1) and immune microenvironment association in laryngeal carcinoma.

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Angiogenesis, programmed death ligand 1 (PD-L1) and immune microenvironment association in laryngeal carcinoma.

PubMed 2021/05/14(内容时间) Pathology Q1 · IF 3.9(JCR 2025)

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中文摘要

在喉鳞状细胞癌(LSCC)这一特定领域,关于血管生成通路与免疫微环境之间相互作用的证据尚未得到探索。鉴于这种相互作用在预后和治疗方面的潜在相关性,本探索性研究的主要目的是调查血管生成(通过 CD31 表达量化)、程序性细胞死亡配体 1(PD-L1)表达与免疫微环境之间是否存在相关性。次要目的是验证与传统的临床病理预后工具相比,综合考虑血管生成和免疫微环境变量是否能提高预后准确性。对 45 例连续 LSCC 病例评估了 CD31 评估的微血管密度(MVD)、以联合阳性评分(CPS)表示的 PD-L1 以及TIL(肿瘤浸润淋巴细胞)(TILs)。Cox 比例风险模型显示,CD31 评估的 MVD 值升高、PD-L1 CPS <1 以及 TILs 计数率 <30% 可预测无病生存期(DFS)缩短。

多因素分析发现,MVD(p<0.0001)和 TILs(p=0.0420)保留了显著的独立预后价值。Spearman 相关模型揭示 CD31 评估的 MVD 值与 PD-L1 CPS 之间存在显著负相关(p=0.0040)。PD-L1 CPS 与 TILs 计数率呈正相关(p<0.0001)。CD31 评估的 MVD >7、PD-L1 CPS <1、TILs <30% 组的 DFS 显著低于 MVD ≤7、PD-L1 CPS ≥1、TILs ≥30% 组(p=0.0001)。这些数据初步支持对 LSCC 中血管生成和免疫微环境标志物预后作用的整合解读。这具有潜在的临床相关性,提示抗血管生成药物与程序性死亡-1/PD-L1 检查点抑制剂联合应用于晚期 LSCC 可能具有协同效应。

展开英文摘要原文

In the specific field of laryngeal carcinoma (LSCC), evidence about the interaction between angiogenetic pathway and immune microenvironment has not yet been explored. Given the potential relevance of such an interaction for prognostic and therapeutic purposes, the main aim of this exploratory study was to investigate the existence of a correlation between angiogenesis (quantified through CD31 expression), programmed cell death ligand 1 (PD-L1) expression, and immune microenvironment. A secondary aim was to verify whether considering a combination of angiogenesis and immune microenvironment variables might improve prognostic accuracy compared to the traditional clinical-pathological prognostic tools. CD31-assessed micro-vessel density (MVD), PD-L1 in terms of combined positive score (CPS), and tumour infiltrating lymphocytes (TILs) were assessed on 45 consecutive cases of LSCC.

Cox proportional hazards model revealed increasing CD31-assessed MVD values, PD-L1 CPS <1, and TILs count rate <30%, as predictive of reduced disease free survival (DFS). Multivariate analysis found that MVD (p<0. 0001) and TILs (p=0. 0420) retained their significant independent prognostic value. Spearman's correlation model disclosed a significant negative correlation between CD31-assessed MVD values and PD-L1 CPS (p=0. 0040). PD-L1 CPS and TILs count rate were positively correlated (p<0.

0001). DFS was significantly lower in the CD31-assessed MVD >7, PD-L1 CPS <1, TILs <30% group than in the MVD ≤7, PD-L1 CPS ≥1, TILs ≥30% group (p=0. 0001). These data preliminarily support an integrated interpretation of the prognostic role or angiogenesis and immune microenvironment markers in LSCC. This is of potential clinical relevance suggesting a synergistic effect of the combination of anti-angiogenic drugs with programmed death-1/PD-L1 checkpoint inhibitors in advanced LSCC.

论文信息

作者
Franz L、Alessandrini L、Calvanese L、Crosetta G、Frigo AC、Marioni G
第一作者单位
Department of Neuroscience DNS, Otolaryngology Section, Padova University, Padova, Italy.Italy
通讯作者单位
Department of Neuroscience DNS, Otolaryngology Section, Padova University, Padova, Italy. Electronic address: gino.marioni@unipd.it.Italy
期刊
Pathology2021 Dec
原文标识
PubMed 33994172 · DOI 10.1016/j.pathol.2021.02.007