46例肺多形性癌PD-L1表达免疫细胞浸润密度与预后的关系

Correlation of PD-L1 expression and the density of immune cell infiltration with prognosis in 46 cases of pulmonary pleomorphic carcinoma

目的:探讨肺多形性癌(pleomorphic carcinoma,PC)不同病理亚型的临床病理特征、肿瘤免疫微环境(tumor immune microenvironment,TIME)及其预后差异,为肺PC患者的分层管理和精准治疗提供依据。方法:回顾性分析内蒙古医科大学附属医院2016年6月至2022年12月收治的46例肺PC患者的临床病理资料,分别对其性别、年龄、肿瘤大小、临床分期、上皮标记物和组织学亚型(混合型和单纯型)等因素进行总生存期(overall survival,OS)的单因素和多因素Cox比例风险回归分析,观察混合型和单纯型组PD-L1表达与免疫细胞浸润特点以及TIME类型。结果:单因素分析显示临床分期(P=0.019)是影响患者OS的危险因素,病理亚型(P=0.048)和中性粒细胞浸润(P=0.007)是影响患者OS的保护因素,多因素分析显示临床分期(P=0.044)和中性粒细胞浸润(P=0.003)是影响患者生存的2个独立因素。肿瘤细胞PD-L1表达和肿瘤免疫微环境分析显示,混合型组CD4+T淋巴细胞浸润密度比单纯型组高(P=0.009),单纯型组PD-L1表达和CD163+M2型肿瘤相关巨噬细胞(tumorassociated macrophages,TAM)浸润密度比混合型组高(P=0.002),混合型组以Ⅱ型和Ⅲ型TIME为主,单纯型组以Ⅰ型和Ⅲ型TIME为主。结论:肺PC具有异质性的形态学和独特的TIME,肺PC应根据形态学和TIME进行分层管理才能提高免疫治疗效果。

Objective:To investigate the clinical and pathological characteristics,tumor immune microenvironment(TIME),and prognostic differences among various pathological subtypes of pulmonary pleomorphic carcinoma(PC),seeking to provide insights for the stratified management and individualized treatment of patients with PC.Methods:A retrospective analysis was conducted on clinical and pathological data from 46 patients with pulmonary PC admitted to the Affiliated Hospital of Inner Mongolia Medical University from June 2016 to December 2022.Univariate and multivariate Cox proportional hazards regression analyses were performed to assess the factors influencing overall survival(OS),including gender,age,tumor size,clinical stage,epithelial markers,and histological subtypes(mixed and pure).The expression of PD-L1,characteristics of immune cell infiltration,and TIME heterogeneity were evaluated in the mixed and pure subtypes.Results:Univariate analysis identified clinical stage(P=0.019)as a risk factor,and pathological subtype(P=0.048)and neutrophil infiltration(P=0.007)as protective factors affecting patient OS.Multivariate analysis confirmed the clinical stage(P=0.044)and neutrophil infiltration(P=0.003)as independent factors influencing patient survival.PD-L1 expression analysis and TIME classification revealed that the mixed subtype exhibited a higher level of CD4+T lymphocyte infiltration than that of the pure subtype(P=0.009).Conversely,compared to the mixed subtype,the pure subtype demonstrated higher expression levels of PD-L1 and greater density of CD163+M2 tumor-associated macrophages(TAM)(P=0.002).The mixed subtype predominantly displayed typeⅡandⅢTIME,while the pure subtype exhibited typeⅠandⅢTIME.Conclusions:Pulmonary PC has heterogeneous morphology and a unique TIME,and stratified management based on morphology and TIME is necessary to improve the effectiveness of immunotherapy.