Guangdong Lung Cancer Institute, Guangdong General Hospital and Guangdong Academy of Medical Sciences, Guangzhou, People's Republic of China; Southern Medical University, Guangzhou, People's Republic of China.
Guangdong Lung Cancer Institute, Guangdong General Hospital and Guangdong Academy of Medical Sciences, Guangzhou, People's Republic of China.
J Thorac Oncol. 2018 Jan;13(1):85-96. doi: 10.1016/j.jtho.2017.10.020. Epub 2017 Nov 7.
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.
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.
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.
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.
肺腺癌（LUAD）的亚型分类将不同的存活率和治疗弱点分开；然而，对于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。
我们对来自 LUAD 公共数据库的 The Cancer Genome Atlas 和 Broad Institute 数据集的发现集以及来自广东肺癌研究所的验证集中的多维数据进行了综合分析。进行免疫组织化学染色以确定程序性细胞死亡 1 配体（PD-L1）和 CD8 的蛋白表达。
与非实性 LUAD 亚型相比，实性为主的 LUAD 患者无病生存期较差，复发/转移频率较高。实性亚型在有吸烟史的患者中更常见。实性为主的 LUAD 仅表现出 PD-L1 的表达增加和 PD-L1-和肿瘤浸润淋巴细胞双重阳性的高比例。同时，在实性亚型的肿瘤中，明显增加了肿瘤突变负担和 GC>TA 颠换的频率。此外，肿瘤的实性亚型表现出活跃的细胞毒性免疫特征，并增加了与免疫原性相关的遗传突变的发生率。
确定实性为主的 LUAD 为一种具有适应性免疫抵抗、更高细胞毒性活性和增强免疫原性的亚型。这些发现表明，实性为主的 LUAD 患者可能代表一个潜在的选择性群体，他们可能受益于辅助程序性细胞死亡 1 阻断免疫治疗。
