Xu Xiaoling, Li Na, Wang Ding, Chen Wei, Fan Yun
Key Laboratory of Head & Neck Cancer Translational Research of Zhejiang Province, Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Hangzhou, China.
Institute of Cancer and Basic Medicine (IBMC), Chinese Academy of Sciences, Hangzhou, China.
Front Oncol. 2021 Jun 24;11:683432. doi: 10.3389/fonc.2021.683432. eCollection 2021.
Invasive mucinous adenocarcinoma (IMA) of the lung is a rare and distinct subtype of adenocarcinoma. At present, people have no idea whether IMA patients can benefit from immunotherapy and target therapy; thus there is an urgent need to clarify the immune microenvironment and genetic characteristics of this cohort.
A total of 31 IMA patients matched with 27 non-mucinous adenocarcinoma (non-IMA) patients were enrolled in this study, and clinical data was collected. The expression of PD-L1, CD8+ tumor-infiltrating lymphocytes (TILs) and ALK was determined by immunohistochemistry. Polymerase Chain Reaction was used to determine the mutations of EGFR. The Chi-square test, Kaplan-Meier method and Cox proportional hazard regression model were used to explore the correlations between these clinicopathological variables, survival and identify risk factors.
Of the patients with IMA 9.7% (3/31) revealed positive PD-L1 expression and 35.5% (11/31) showed CD8+ TIL infiltration, which were markedly lower than that of non-IMA group [PD-L1: 48.1% (13/27); CD8: 81.5% (22/27)]. Moreover, five (16.1%) patients in IMA group and 10 (37.0%) patients in non-IMA group had EGFR mutations, and nine (29.0%) patients in IMA group and zero (0.0%) patient in non-IMA group had ALK rearrangements. Additionally, we observed that IMA patients with CD8+ TIL infiltration had a worse prognosis than CD8-negative group (P = 0.024). Multivariate analyses showed that CD8 was an independent prognostic factor for patient's survival (HR = 5.60, 95% CI: 1.35-23.22, P = 0.017).
Patients with IMA have down-regulated expression of PD-L1 and less CD8+ TIL infiltration in tumor microenvironment. Besides, a lower frequency of EGFR mutations was detected in patients with IMA than non-IMA patients while a higher rate of ALK rearrangements was found. Our results provide important reference for therapy of lung IMA.
肺浸润性黏液腺癌（IMA）是腺癌中一种罕见且独特的亚型。目前，人们尚不清楚IMA患者是否能从免疫治疗和靶向治疗中获益；因此，迫切需要阐明该队列的免疫微环境和基因特征。
本研究共纳入31例IMA患者，并与27例非黏液腺癌（非IMA）患者进行匹配，收集临床数据。采用免疫组织化学法检测PD-L1、CD8 +肿瘤浸润淋巴细胞（TILs）和ALK的表达。采用聚合酶链反应检测EGFR的突变情况。采用卡方检验、Kaplan-Meier法和Cox比例风险回归模型探讨这些临床病理变量与生存之间的相关性，并确定危险因素。
IMA患者中9.7%（3/31）显示PD-L1表达阳性，35.5%（11/31）显示CD8 + TIL浸润，明显低于非IMA组[PD-L1：48.1%（13/27）；CD8：81.5%（22/27）]。此外，IMA组5例（16.1%）患者和非IMA组10例（37.0%）患者有EGFR突变，IMA组9例（29.0%）患者和非IMA组0例（0.0%）患者有ALK重排。此外，我们观察到CD8 + TIL浸润的IMA患者预后比CD8阴性组更差（P = 0.024）。多因素分析显示，CD8是患者生存的独立预后因素（HR = 5.60，95% CI：1.35 - 23.22，P = 0.017）。
IMA患者肿瘤微环境中PD-L1表达下调，CD8 + TIL浸润较少。此外，与非IMA患者相比，IMA患者检测到EGFR突变的频率较低，而ALK重排的发生率较高。我们的结果为肺IMA的治疗提供了重要参考。
