Profiling Tumor Immune Microenvironment of Non-Small Cell Lung Cancer Using Multiplex Immunofluorescence
This study attempted to profile the tumor immune microenvironment (TIME) of non-small cell lung cancer (NSCLC) by multiplex immunofluorescence of 681 NSCLC cases. The number, density, and proportion of 26 types of immune cells in tumor nest and tumor stroma were evaluated, revealing some close inter...
Guardado en:
Autores principales: | , , , , , , , , , , , , , , , , |
---|---|
Formato: | article |
Lenguaje: | EN |
Publicado: |
Frontiers Media S.A.
2021
|
Materias: | |
Acceso en línea: | https://doaj.org/article/6d6bb725d825440b8850bb850a747197 |
Etiquetas: |
Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
|
id |
oai:doaj.org-article:6d6bb725d825440b8850bb850a747197 |
---|---|
record_format |
dspace |
spelling |
oai:doaj.org-article:6d6bb725d825440b8850bb850a7471972021-11-04T09:12:39ZProfiling Tumor Immune Microenvironment of Non-Small Cell Lung Cancer Using Multiplex Immunofluorescence1664-322410.3389/fimmu.2021.750046https://doaj.org/article/6d6bb725d825440b8850bb850a7471972021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fimmu.2021.750046/fullhttps://doaj.org/toc/1664-3224This study attempted to profile the tumor immune microenvironment (TIME) of non-small cell lung cancer (NSCLC) by multiplex immunofluorescence of 681 NSCLC cases. The number, density, and proportion of 26 types of immune cells in tumor nest and tumor stroma were evaluated, revealing some close interactions particularly between intrastromal neutrophils and intratumoral regulatory T cells (Treg) (r2 = 0.439, P < 0.001), intrastromal CD4+CD38+ T cells and CD20-positive B cells (r2 = 0.539, P < 0.001), and intratumoral CD8-positive T cells and M2 macrophages expressing PD-L1 (r2 = 0.339, P < 0.001). Three immune subtypes correlated with distinct immune characteristics were identified using the unsupervised consensus clustering approach. The immune-activated subtype had the longest disease-free survival (DFS) and demonstrated the highest infiltration of CD4-positive T cells, CD8-positive T cells, and CD20-positive B cells. The immune-defected subtype was rich in cancer stem cells and macrophages, and these patients had the worst prognosis. The immune-exempted subtype had the highest levels of neutrophils and Tregs. Intratumoral CD68-positive macrophages, M1 macrophages, and intrastromal CD4+ cells, CD4+FOXP3- cells, CD8+ cells, and PD-L1+ cells were further found to be the most robust prognostic biomarkers for DFS, which were used to construct and validate the immune-related risk score for risk stratification (high vs. median vs. low) and the prediction of 5-year DFS rates (23.2% vs. 37.9% vs. 43.1%, P < 0.001). In conclusion, the intricate and intrinsic structure of TIME in NSCLC was demonstrated, showing potency in subtyping and prognostication.Haoxin PengHaoxin PengXiangrong WuXiangrong WuRan ZhongRan ZhongTao YuXiuyu CaiJun LiuYaokai WenYaokai WenYiyuan AoYiyuan AoJiana ChenJiana ChenYutian LiYutian LiMiao HeCaichen LiHongbo ZhengYanhui ChenYanhui ChenZhenkui PanJianxing HeWenhua LiangWenhua LiangFrontiers Media S.A.articletumor immune microenvironmentimmune landscapeimmune subtypingmultiplex immunofluorescenceimmune-related risk scoreImmunologic diseases. AllergyRC581-607ENFrontiers in Immunology, Vol 12 (2021) |
institution |
DOAJ |
collection |
DOAJ |
language |
EN |
topic |
tumor immune microenvironment immune landscape immune subtyping multiplex immunofluorescence immune-related risk score Immunologic diseases. Allergy RC581-607 |
spellingShingle |
tumor immune microenvironment immune landscape immune subtyping multiplex immunofluorescence immune-related risk score Immunologic diseases. Allergy RC581-607 Haoxin Peng Haoxin Peng Xiangrong Wu Xiangrong Wu Ran Zhong Ran Zhong Tao Yu Xiuyu Cai Jun Liu Yaokai Wen Yaokai Wen Yiyuan Ao Yiyuan Ao Jiana Chen Jiana Chen Yutian Li Yutian Li Miao He Caichen Li Hongbo Zheng Yanhui Chen Yanhui Chen Zhenkui Pan Jianxing He Wenhua Liang Wenhua Liang Profiling Tumor Immune Microenvironment of Non-Small Cell Lung Cancer Using Multiplex Immunofluorescence |
description |
This study attempted to profile the tumor immune microenvironment (TIME) of non-small cell lung cancer (NSCLC) by multiplex immunofluorescence of 681 NSCLC cases. The number, density, and proportion of 26 types of immune cells in tumor nest and tumor stroma were evaluated, revealing some close interactions particularly between intrastromal neutrophils and intratumoral regulatory T cells (Treg) (r2 = 0.439, P < 0.001), intrastromal CD4+CD38+ T cells and CD20-positive B cells (r2 = 0.539, P < 0.001), and intratumoral CD8-positive T cells and M2 macrophages expressing PD-L1 (r2 = 0.339, P < 0.001). Three immune subtypes correlated with distinct immune characteristics were identified using the unsupervised consensus clustering approach. The immune-activated subtype had the longest disease-free survival (DFS) and demonstrated the highest infiltration of CD4-positive T cells, CD8-positive T cells, and CD20-positive B cells. The immune-defected subtype was rich in cancer stem cells and macrophages, and these patients had the worst prognosis. The immune-exempted subtype had the highest levels of neutrophils and Tregs. Intratumoral CD68-positive macrophages, M1 macrophages, and intrastromal CD4+ cells, CD4+FOXP3- cells, CD8+ cells, and PD-L1+ cells were further found to be the most robust prognostic biomarkers for DFS, which were used to construct and validate the immune-related risk score for risk stratification (high vs. median vs. low) and the prediction of 5-year DFS rates (23.2% vs. 37.9% vs. 43.1%, P < 0.001). In conclusion, the intricate and intrinsic structure of TIME in NSCLC was demonstrated, showing potency in subtyping and prognostication. |
format |
article |
author |
Haoxin Peng Haoxin Peng Xiangrong Wu Xiangrong Wu Ran Zhong Ran Zhong Tao Yu Xiuyu Cai Jun Liu Yaokai Wen Yaokai Wen Yiyuan Ao Yiyuan Ao Jiana Chen Jiana Chen Yutian Li Yutian Li Miao He Caichen Li Hongbo Zheng Yanhui Chen Yanhui Chen Zhenkui Pan Jianxing He Wenhua Liang Wenhua Liang |
author_facet |
Haoxin Peng Haoxin Peng Xiangrong Wu Xiangrong Wu Ran Zhong Ran Zhong Tao Yu Xiuyu Cai Jun Liu Yaokai Wen Yaokai Wen Yiyuan Ao Yiyuan Ao Jiana Chen Jiana Chen Yutian Li Yutian Li Miao He Caichen Li Hongbo Zheng Yanhui Chen Yanhui Chen Zhenkui Pan Jianxing He Wenhua Liang Wenhua Liang |
author_sort |
Haoxin Peng |
title |
Profiling Tumor Immune Microenvironment of Non-Small Cell Lung Cancer Using Multiplex Immunofluorescence |
title_short |
Profiling Tumor Immune Microenvironment of Non-Small Cell Lung Cancer Using Multiplex Immunofluorescence |
title_full |
Profiling Tumor Immune Microenvironment of Non-Small Cell Lung Cancer Using Multiplex Immunofluorescence |
title_fullStr |
Profiling Tumor Immune Microenvironment of Non-Small Cell Lung Cancer Using Multiplex Immunofluorescence |
title_full_unstemmed |
Profiling Tumor Immune Microenvironment of Non-Small Cell Lung Cancer Using Multiplex Immunofluorescence |
title_sort |
profiling tumor immune microenvironment of non-small cell lung cancer using multiplex immunofluorescence |
publisher |
Frontiers Media S.A. |
publishDate |
2021 |
url |
https://doaj.org/article/6d6bb725d825440b8850bb850a747197 |
work_keys_str_mv |
AT haoxinpeng profilingtumorimmunemicroenvironmentofnonsmallcelllungcancerusingmultipleximmunofluorescence AT haoxinpeng profilingtumorimmunemicroenvironmentofnonsmallcelllungcancerusingmultipleximmunofluorescence AT xiangrongwu profilingtumorimmunemicroenvironmentofnonsmallcelllungcancerusingmultipleximmunofluorescence AT xiangrongwu profilingtumorimmunemicroenvironmentofnonsmallcelllungcancerusingmultipleximmunofluorescence AT ranzhong profilingtumorimmunemicroenvironmentofnonsmallcelllungcancerusingmultipleximmunofluorescence AT ranzhong profilingtumorimmunemicroenvironmentofnonsmallcelllungcancerusingmultipleximmunofluorescence AT taoyu profilingtumorimmunemicroenvironmentofnonsmallcelllungcancerusingmultipleximmunofluorescence AT xiuyucai profilingtumorimmunemicroenvironmentofnonsmallcelllungcancerusingmultipleximmunofluorescence AT junliu profilingtumorimmunemicroenvironmentofnonsmallcelllungcancerusingmultipleximmunofluorescence AT yaokaiwen profilingtumorimmunemicroenvironmentofnonsmallcelllungcancerusingmultipleximmunofluorescence AT yaokaiwen profilingtumorimmunemicroenvironmentofnonsmallcelllungcancerusingmultipleximmunofluorescence AT yiyuanao profilingtumorimmunemicroenvironmentofnonsmallcelllungcancerusingmultipleximmunofluorescence AT yiyuanao profilingtumorimmunemicroenvironmentofnonsmallcelllungcancerusingmultipleximmunofluorescence AT jianachen profilingtumorimmunemicroenvironmentofnonsmallcelllungcancerusingmultipleximmunofluorescence AT jianachen profilingtumorimmunemicroenvironmentofnonsmallcelllungcancerusingmultipleximmunofluorescence AT yutianli profilingtumorimmunemicroenvironmentofnonsmallcelllungcancerusingmultipleximmunofluorescence AT yutianli profilingtumorimmunemicroenvironmentofnonsmallcelllungcancerusingmultipleximmunofluorescence AT miaohe profilingtumorimmunemicroenvironmentofnonsmallcelllungcancerusingmultipleximmunofluorescence AT caichenli profilingtumorimmunemicroenvironmentofnonsmallcelllungcancerusingmultipleximmunofluorescence AT hongbozheng profilingtumorimmunemicroenvironmentofnonsmallcelllungcancerusingmultipleximmunofluorescence AT yanhuichen profilingtumorimmunemicroenvironmentofnonsmallcelllungcancerusingmultipleximmunofluorescence AT yanhuichen profilingtumorimmunemicroenvironmentofnonsmallcelllungcancerusingmultipleximmunofluorescence AT zhenkuipan profilingtumorimmunemicroenvironmentofnonsmallcelllungcancerusingmultipleximmunofluorescence AT jianxinghe profilingtumorimmunemicroenvironmentofnonsmallcelllungcancerusingmultipleximmunofluorescence AT wenhualiang profilingtumorimmunemicroenvironmentofnonsmallcelllungcancerusingmultipleximmunofluorescence AT wenhualiang profilingtumorimmunemicroenvironmentofnonsmallcelllungcancerusingmultipleximmunofluorescence |
_version_ |
1718444965917360128 |