Department of Neuroscience DNS, Otolaryngology Section, Padova University, Padova, Italy.
Department of Medicine DIMED, Padova University, Padova, Italy.
Pathology. 2021 Dec;53(7):844-851. doi: 10.1016/j.pathol.2021.02.007. Epub 2021 May 14.
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.
在喉癌（LSCC）的特定领域，关于血管生成途径和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测和治疗方面的潜在相关性，本探索性研究的主要目的是研究血管生成（通过 CD31 表达来量化）、程序性细胞死亡配体 1（PD-L1）表达和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，同时考虑血管生成和免疫微环境变量是否可以提高预后准确性。在 45 例连续的 LSCC 病例中评估了 CD31 评估的微血管密度（MVD）、PD-L1 的联合阳性评分（CPS）和肿瘤浸润淋巴细胞（TIL）。Cox 比例风险模型显示，CD31 评估的 MVD 值增加、PD-L1 CPS<1 和 TIL 计数率<30%，是疾病无进展生存期（DFS）降低的预测因素。多变量分析发现 MVD（p<0.0001）和 TIL（p=0.0420）保留了其显著的独立预后价值。Spearman 相关性模型显示 CD31 评估的 MVD 值与 PD-L1 CPS 之间存在显著的负相关（p=0.0040）。PD-L1 CPS 和 TIL 计数率呈正相关（p<0.0001）。与 MVD≤7、PD-L1 CPS≥1、TIL≥30%组相比，MVD>7、PD-L1 CPS<1、TIL<30%组的 DFS 显著降低（p=0.0001）。这些数据初步支持了对 LSCC 中血管生成和免疫微环境标志物的预后作用的综合解释。这具有潜在的临床相关性，表明在晚期 LSCC 中联合使用抗血管生成药物和程序性死亡-1/PD-L1 检查点抑制剂具有协同作用。
