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...

Descripción completa

Guardado en:
Detalles Bibliográficos
Autores principales: Haoxin Peng, Xiangrong Wu, Ran Zhong, Tao Yu, Xiuyu Cai, Jun Liu, Yaokai Wen, Yiyuan Ao, Jiana Chen, Yutian Li, Miao He, Caichen Li, Hongbo Zheng, Yanhui Chen, Zhenkui Pan, Jianxing He, Wenhua Liang
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