Characterization of evolution trajectory and immune profiling of brain metastasis in lung adenocarcinoma

Abstract Characterizing the evolutionary trajectory and immune profiling of brain metastasis (BM) may provide insights in the development of novel therapeutic strategies. Here, we performed whole-exome sequencing and multiplex immunofluorescence (MIF) of 40 samples from 12 lung adenocarcinoma (LUAD)...

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Autores principales:	Tao Jiang, Yan Yan, Kun Zhou, Chunxia Su, Shengxiang Ren, Nan Li, Likun Hou, Xianchao Guo, Wei Zhu, Henghui Zhang, Jie Lin, Jun Zhang, Caicun Zhou
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/6d2e59364f27463d934d2e5d07bbf326
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spelling	oai:doaj.org-article:6d2e59364f27463d934d2e5d07bbf3262021-12-02T14:23:49ZCharacterization of evolution trajectory and immune profiling of brain metastasis in lung adenocarcinoma10.1038/s41698-021-00151-w2397-768Xhttps://doaj.org/article/6d2e59364f27463d934d2e5d07bbf3262021-02-01T00:00:00Zhttps://doi.org/10.1038/s41698-021-00151-whttps://doaj.org/toc/2397-768XAbstract Characterizing the evolutionary trajectory and immune profiling of brain metastasis (BM) may provide insights in the development of novel therapeutic strategies. Here, we performed whole-exome sequencing and multiplex immunofluorescence (MIF) of 40 samples from 12 lung adenocarcinoma (LUAD) patients with BM and compared to their paired primary tumors. We observed significantly higher intertumor heterogeneity between paired primary tumors and BMs, with only a median of 8.3% of genetic mutations identified as shared. Phylogenetic analysis revealed that BM-competent clones genetically diverged from their primary tumors at relatively early stage, suggesting that the parallel progression model is dominant. In cases with synchronous lymph node metastasis (LNM), phylogenetic analysis suggested that BM is a later event than LNM. MIF analysis found that BMs exhibited significantly lower CD8+ T cell infiltration (P = 0.048), and elevated CD4+Foxp3+ T cell infiltration (P = 0.036) and PD-1 expression (P = 0.047) in comparison to the matched primary tumors, indicating an immunosuppressive microenvironment in BMs. The current study revealed the discrepancy of mutational landscape as well as tumor immune microenvironment between BM and its primary tumor – such findings shall help us better understand the unique biological features of BM and develop innovative strategies accordingly for our patients with LUAD.Tao JiangYan YanKun ZhouChunxia SuShengxiang RenNan LiLikun HouXianchao GuoWei ZhuHenghui ZhangJie LinJun ZhangCaicun ZhouNature PortfolioarticleNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENnpj Precision Oncology, Vol 5, Iss 1, Pp 1-9 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Tao Jiang Yan Yan Kun Zhou Chunxia Su Shengxiang Ren Nan Li Likun Hou Xianchao Guo Wei Zhu Henghui Zhang Jie Lin Jun Zhang Caicun Zhou Characterization of evolution trajectory and immune profiling of brain metastasis in lung adenocarcinoma
description	Abstract Characterizing the evolutionary trajectory and immune profiling of brain metastasis (BM) may provide insights in the development of novel therapeutic strategies. Here, we performed whole-exome sequencing and multiplex immunofluorescence (MIF) of 40 samples from 12 lung adenocarcinoma (LUAD) patients with BM and compared to their paired primary tumors. We observed significantly higher intertumor heterogeneity between paired primary tumors and BMs, with only a median of 8.3% of genetic mutations identified as shared. Phylogenetic analysis revealed that BM-competent clones genetically diverged from their primary tumors at relatively early stage, suggesting that the parallel progression model is dominant. In cases with synchronous lymph node metastasis (LNM), phylogenetic analysis suggested that BM is a later event than LNM. MIF analysis found that BMs exhibited significantly lower CD8+ T cell infiltration (P = 0.048), and elevated CD4+Foxp3+ T cell infiltration (P = 0.036) and PD-1 expression (P = 0.047) in comparison to the matched primary tumors, indicating an immunosuppressive microenvironment in BMs. The current study revealed the discrepancy of mutational landscape as well as tumor immune microenvironment between BM and its primary tumor – such findings shall help us better understand the unique biological features of BM and develop innovative strategies accordingly for our patients with LUAD.
format	article
author	Tao Jiang Yan Yan Kun Zhou Chunxia Su Shengxiang Ren Nan Li Likun Hou Xianchao Guo Wei Zhu Henghui Zhang Jie Lin Jun Zhang Caicun Zhou
author_facet	Tao Jiang Yan Yan Kun Zhou Chunxia Su Shengxiang Ren Nan Li Likun Hou Xianchao Guo Wei Zhu Henghui Zhang Jie Lin Jun Zhang Caicun Zhou
author_sort	Tao Jiang
title	Characterization of evolution trajectory and immune profiling of brain metastasis in lung adenocarcinoma
title_short	Characterization of evolution trajectory and immune profiling of brain metastasis in lung adenocarcinoma
title_full	Characterization of evolution trajectory and immune profiling of brain metastasis in lung adenocarcinoma
title_fullStr	Characterization of evolution trajectory and immune profiling of brain metastasis in lung adenocarcinoma
title_full_unstemmed	Characterization of evolution trajectory and immune profiling of brain metastasis in lung adenocarcinoma
title_sort	characterization of evolution trajectory and immune profiling of brain metastasis in lung adenocarcinoma
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/6d2e59364f27463d934d2e5d07bbf326
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Characterization of evolution trajectory and immune profiling of brain metastasis in lung adenocarcinoma

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