Immune microenvironment composition in non-small cell lung cancer and its association with survival

Immune microenvironment composition in non-small cell lung cancer and its association with survival
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DOI:
10.1002/cti2.1142
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发表时间:
2020-01-01
影响因子:
5.8
通讯作者:
Groen, Harry J. M.
Groen, Harry J. M.
中科院分区:
医学3区
文献类型:
--
作者:
Tamminga, Menno;Hiltermann, Thijo Jeroen N.;Groen, Harry J. M.

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目的在非小细胞肺癌(NSCLC)中,免疫系统及其组成可能影响生存。在这项计算机研究中,对NSCLC患者的免疫浸润成分进行了评价。方法从GEO数据库中获取早期NSCLC患者肿瘤组织的基因表达数据。使用CIBERSORT,估计了22种免疫细胞级分。结果1430例治疗前非小细胞肺癌患者的免疫浸润主要含有浆细胞、巨噬细胞和CD 8 T细胞。较高比例的静息肥大细胞和CD 4辅助性T细胞与较长的总生存期相关(HR = 0.95,P < 0.01; HR = 0.98,P = 0.04),较高比例的M2巨噬细胞和活性树突状细胞与较短的生存期相关(HR = 1.02,P = 0.03; HR = 1.03,P = 0.05)。有生存数据的腺癌患者(n = 587)的静息肥大和静息CD 4 T细胞比例高于鳞癌患者(n = 254),M0巨噬细胞比例低于鳞癌患者(n = 254),与OS相关(HR分别为0.95,P = 0.04; HR = 0.97,P = 0.01; HR = 1.03,P = 0.01)。记忆B细胞、初始CD 4 T细胞和中性粒细胞的分数根据亚型与存活率有不同的关联。吸烟者外周血中调节性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,与生存期较短相关(HR = 1.3,P < 0.01; HR = 1.13,P = 0.02; HR = 1.09,P = 0.03; HR = 1.04,P = 0.02)。结论非小细胞肺癌患者治疗前免疫细胞组成的差异与生存相关,并取决于吸烟状况和组织学亚型。吸烟者的免疫组成与较低的生存率有关。
Objectives In non-small cell lung cancer (NSCLC), the immune system and possibly its composition affect survival. In thisin silicostudy, the immune infiltrate composition in NSCLC patients was evaluated. Methods Gene expression data of tumors from early NSCLC patients were obtained from Gene Expression Omnibus (GEO). With CIBERSORT, 22 immune cell fractions were estimated. Results 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,P < 0.01; HR = 0.98, = 0.04, respectively) and higher fractions of M2 macrophages and active dendritic cells with shorter survival (HR = 1.02,P = 0.03; HR = 1.03,P = 0.05, respectively). Adenocarcinoma patients with survival data (n = 587) showed higher fractions of resting mast and resting CD4 T cells, and lower M0 macrophages than squamous cell carcinoma (n = 254), which were associated with OS (HR = 0.95,P = 0.04; HR = 0.97,P = 0.01; HR = 1.03,P = 0.01, respectively). Fractions of memory B cells, naive 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,P < 0.01; HR = 1.13,P = 0.02; HR = 1.09,P = 0.03; HR = 1.04,P = 0.02, respectively). Conclusion 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.