Tamminga Menno, Hiltermann Thijo Jeroen N, Schuuring Ed, Timens Wim, Fehrmann Rudolf Sn, Groen Harry Jm
Department of Pulmonary Diseases University Medical Center Groningen University of Groningen Groningen The Netherlands.
Department of Pathology and Medical Biology University Medical Center Groningen University of Groningen Groningen The Netherlands.
Clin Transl Immunology. 2020 Jun 12;9(6):e1142. doi: 10.1002/cti2.1142. eCollection 2020.
In non-small cell lung cancer (NSCLC), the immune system and possibly its composition affect survival. In this study, the immune infiltrate composition in NSCLC patients was evaluated.
Gene expression data of tumors from early NSCLC patients were obtained from Gene Expression Omnibus (GEO). With CIBERSORT, 22 immune cell fractions were estimated.
The immune infiltrate of 1430 pretreatment NSCLC patients contained mostly plasma cells, macrophages and CD8 T cells. Higher fractions of resting mast and CD4 T-helper cells were associated with longer overall survival (OS) (HR = 0.95, < 0.01; HR = 0.98, = 0.04, respectively) and higher fractions of M2 macrophages and active dendritic cells with shorter survival (HR = 1.02, 0.03; HR = 1.03, 0.05, respectively). Adenocarcinoma patients with survival data ( = 587) showed higher fractions of resting mast and resting CD4 T cells, and lower M0 macrophages than squamous cell carcinoma ( = 254), which were associated with OS (HR = 0.95, 0.04; HR = 0.97, 0.01; HR = 1.03, 0.01, respectively). Fractions of memory B cells, naïve CD4 T cells and neutrophils had different associations with survival depending on the subtype. Smokers had had higher fractions of regulatory T cell, follicular helper T cell, neutrophil and M2 macrophage, which were associated with shorter survival (HR = 1.3, < 0.01; HR = 1.13, 0.02; HR = 1.09, 0.03; HR = 1.04, 0.02, respectively).
Pretreatment differences in immune cell composition in NSCLC are associated with survival and depend on smoking status and histological subtype. Smokers' immune composition is associated with lower survival.
在非小细胞肺癌（NSCLC）中，免疫系统及其组成可能会影响生存率。在本研究中，对NSCLC患者的免疫浸润成分进行了评估。
从基因表达综合数据库（GEO）中获取早期NSCLC患者肿瘤的基因表达数据。使用CIBERSORT估算22种免疫细胞成分。
1430例NSCLC患者治疗前的免疫浸润主要包含浆细胞、巨噬细胞和CD8 T细胞。静息肥大细胞和CD4辅助性T细胞比例较高与总生存期（OS）较长相关（HR分别为0.95，P<0.01；HR为0.98，P = 0.04），而M2巨噬细胞和活化树突状细胞比例较高与生存期较短相关（HR分别为1.02，P = 0.03；HR为1.03，P = 0.05）。有生存数据的腺癌患者（n = 587）静息肥大细胞和静息CD4 T细胞比例高于鳞状细胞癌患者（n = 254），M0巨噬细胞比例低于鳞状细胞癌患者，这些均与OS相关（HR分别为0.95，P = 0.04；HR为0.97，P = 0.01；HR为1.03，P = 0.01）。记忆B细胞、初始CD4 T细胞和中性粒细胞的比例与生存的关联因亚型而异。吸烟者调节性T细胞、滤泡辅助性T细胞、中性粒细胞和M2巨噬细胞比例较高，这些与生存期较短相关（HR分别为1.3，P<0.01；HR为1.13，P = 0.02；HR为1.09，P = 0.03；HR为1.04，P = 0.02）。
NSCLC患者治疗前免疫细胞组成的差异与生存相关，且取决于吸烟状态和组织学亚型。吸烟者的免疫组成与较低的生存率相关。
