Introduction Subtype classification of lung adenocarcinoma (LUAD) divides different survivals and therapeutic vulnerabilities; however, little is known about the disease’s underlying molecular mechanism. This study sought to determine the genetic and immune profiles of histologic subtypes and identify the evidence for adjuvant immunotherapy. Methods We performed an integrated analysis of multidimensional data from a discovery set consisting of cohorts of The Cancer Genome Atlas and the Broad Institute data set from the LUAD public database and a validation set from the Guangdong Lung Cancer Institute. Immunohistochemical staining was carried out to determine the expression of the proteins programmed cell death 1 ligand (PD‐L1) and CD8. Results Patients with solid predominant LUAD showed poor disease‐free survival and a high frequency of relapse/metastasis compared with those with the nonsolid subtype of LUAD. The solid subtype tended to occur more frequently in those with a history of smoking. Solid predominant LUAD exclusively showed increased expression of PD‐L1 and a high proportion of dual positive PD‐L1– and tumor‐infiltrating lymphocytes. Meanwhile, a notable increase in the tumor mutation burden and higher frequency of GC>TA transversions were specifically identified in tumors of the solid subtype. Furthermore, the solid subtype of tumor displayed an active cytotoxic immune signature and increased incidence of genetic mutations related to immunogenicity. Conclusion Solid predominant LUAD was identified as a subtype with adaptive immune resistance, higher cytotoxic activity, and enhanced immunogenicity. These findings suggest that patients with solid predominant LUAD may represent a potential selective group that will benefit from adjuvant programmed cell death 1 blockade immunotherapy.

中文翻译：

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实体为主的肺腺癌的遗传和免疫特征揭示了潜在的免疫治疗策略

介绍 肺腺癌 (LUAD) 的亚型分类划分了不同的存活率和治疗脆弱性；然而，对该疾病的潜在分子机制知之甚少。本研究旨在确定组织学亚型的遗传和免疫特征，并确定辅助免疫治疗的证据。方法 我们对来自 LUAD 公共数据库的癌症基因组图谱和 Broad Institute 数据集的队列以及广东肺癌研究所的验证集组成的发现集进行了多维数据的综合分析。进行免疫组织化学染色以确定蛋白质程序性细胞死亡 1 配体 (PD-L1) 和 CD8 的表达。结果 与非实体型 LUAD 患者相比，实体型 LUAD 患者的无病生存期较差，复发/转移频率高。在有吸烟史的人中，实体亚型的发生频率更高。实性优势 LUAD 仅显示 PD-L1 表达增加和高比例的双阳性 PD-L1 和肿瘤浸润淋巴细胞。同时，在实体亚型的肿瘤中特异性地发现了肿瘤突变负荷的显着增加和更高频率的 GC>TA 颠换。此外，肿瘤的实体亚型显示出活跃的细胞毒性免疫特征和与免疫原性相关的基因突变的发生率增加。结论 实体优势型 LUAD 被鉴定为具有适应性免疫抵抗的亚型，更高的细胞毒活性和增强的免疫原性。这些发现表明，以实体为主的 LUAD 患者可能代表了一个潜在的选择性群体，他们将从辅助程序性细胞死亡 1 阻断免疫疗法中受益。