免疫检查点抑制剂在肺淋巴上皮瘤样癌等病毒相关肿瘤中的研究进展

Research Progress of Immune Checkpoint Inhibitors in Virus-Associated Cancer Such as Pulmonary Lymphoepithelioma-Like Carcinoma

肺淋巴上皮瘤样癌(pulmonary lymphoepithelioma-like carcinoma,PLELC)是一种罕见的肺原发恶性肿瘤,较其他类型的非小细胞肺癌具有更好的预后。EB病毒(Epstein-Barr virus,EBV)感染已被证实和这种特殊类型肺部恶性肿瘤的发生发展有重要联系。目前PLELC的标准治疗仍存在争议,而免疫治疗在病毒相关性肿瘤的治疗中呈现出良好的治疗效果,包括人乳头瘤病毒阳性的头颈部鳞状细胞癌和EBV阳性的胃癌等。由于和EBV感染相关,程序性死亡配体-1(programmed death ligand 1,PD-L1)高表达和肿瘤区域大量淋巴细胞浸润,免疫治疗可能对PLELC产生良好的治疗效果。在本文中,我们将从EBV感染和PLELC的关系,免疫检查点抑制剂在这种特殊类型肿瘤中的治疗效果和其治疗产生耐药的机制这几方面进行阐述。

Pulmonary lymphoepithelioma-like carcinoma(PLELC)was a rare type of primary malignant lung tumor with favorable prognosis than other types of non-small cell lung cancer.Since its first publication in 1987,a close association between the disease and Epstein-Barr virus(EBV)infection had been found.To date,no standard therapeutic strategy for this rare disease had been established.It was reported that immunotherapy had a good therapeutic effect in some virus-associated cancers,including human papilloma virus(HPV)-positive head and neck squamous cell carcinoma and EBV-positive gastric cancer.For its association with EBV infection,overexpression of programmed death ligand 1(PD-L1)and sufficient lymphocytic infiltration,it was likely that immunotherapy could be a promising choice for PLELC.In this review,we retrospected the association of EBV and PLELC,described the therapeutic effects of immune checkpoint inhibitors in this rare disease and explore drug resistance mechanisms to immune checkpoint inhibitors.