Unraveling the immune mechanisms and therapeutic targets in lung adenosquamous transformation

Adenocarcinoma-to-squamous cell carcinoma transformation (AST) induces drug resistance in patients with lung adenocarcinoma (LUAD), often resulting in unfavorable clinical outcomes. In recent years, it has been found that alterations in the tumor immune microenvironment (TIME) during adenosquamous c...

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Main Authors: Haiyan Xu, Ying Yang, PingLi Wang, Shengnan Lin, Xiaochun Zhang, Huiwen Ni, Zhiyong Xu
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-06-01
Series:Frontiers in Immunology
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Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2025.1542526/full
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author Haiyan Xu
Ying Yang
PingLi Wang
Shengnan Lin
Xiaochun Zhang
Huiwen Ni
Zhiyong Xu
Zhiyong Xu
author_facet Haiyan Xu
Ying Yang
PingLi Wang
Shengnan Lin
Xiaochun Zhang
Huiwen Ni
Zhiyong Xu
Zhiyong Xu
author_sort Haiyan Xu
collection DOAJ
description Adenocarcinoma-to-squamous cell carcinoma transformation (AST) induces drug resistance in patients with lung adenocarcinoma (LUAD), often resulting in unfavorable clinical outcomes. In recent years, it has been found that alterations in the tumor immune microenvironment (TIME) during adenosquamous carcinoma trans-differentiation also influence the efficacy of immunotherapy. Moreover, the aberrant expression and activation of several driver genes for AST lead to abnormal infiltration and function of immune cell by remodeling the cellular inflammatory phenotype. In this review, we will systematically present the changes in the TIME and molecular regulatory mechanisms during adenosquamous carcinoma differentiation, aiming to gain a better understand of the function of immune cells during this process and the potential value of combining immunotherapy to enhance the treatment of non-small cell lung cancer (NSCLC).
format Article
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institution DOAJ
issn 1664-3224
language English
publishDate 2025-06-01
publisher Frontiers Media S.A.
record_format Article
series Frontiers in Immunology
spelling doaj-art-666db45be0c94e71b3b4d7e8be73682d2025-08-20T03:10:46ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-06-011610.3389/fimmu.2025.15425261542526Unraveling the immune mechanisms and therapeutic targets in lung adenosquamous transformationHaiyan Xu0Ying Yang1PingLi Wang2Shengnan Lin3Xiaochun Zhang4Huiwen Ni5Zhiyong Xu6Zhiyong Xu7Department of Biobank, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, ChinaDepartment of Respiratory and Critical Care Medicine, The Fourth Affiliated Hospital of Zhejiang University School of Medicine, Yiwu, ChinaDepartment of Respiratory and Critical Care Medicine, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, ChinaDepartment of Biobank, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, ChinaDepartment of Biobank, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, ChinaDepartment of Biobank, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, ChinaDepartment of Respiratory and Critical Care Medicine, The Fourth Affiliated Hospital of Zhejiang University School of Medicine, Yiwu, ChinaBreast Cancer Center, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine, Chinese Academy of Sciences, Hangzhou, ChinaAdenocarcinoma-to-squamous cell carcinoma transformation (AST) induces drug resistance in patients with lung adenocarcinoma (LUAD), often resulting in unfavorable clinical outcomes. In recent years, it has been found that alterations in the tumor immune microenvironment (TIME) during adenosquamous carcinoma trans-differentiation also influence the efficacy of immunotherapy. Moreover, the aberrant expression and activation of several driver genes for AST lead to abnormal infiltration and function of immune cell by remodeling the cellular inflammatory phenotype. In this review, we will systematically present the changes in the TIME and molecular regulatory mechanisms during adenosquamous carcinoma differentiation, aiming to gain a better understand of the function of immune cells during this process and the potential value of combining immunotherapy to enhance the treatment of non-small cell lung cancer (NSCLC).https://www.frontiersin.org/articles/10.3389/fimmu.2025.1542526/fulladenosquamous lung carcinoma (ASLC)adenocarcinoma-to-squamous cell carcinoma transformation (AST)tumor immune microenvironment (TIME)tumor-associated macrophages (TAMs)tumor-associated neutrophils (TANs)
spellingShingle Haiyan Xu
Ying Yang
PingLi Wang
Shengnan Lin
Xiaochun Zhang
Huiwen Ni
Zhiyong Xu
Zhiyong Xu
Unraveling the immune mechanisms and therapeutic targets in lung adenosquamous transformation
Frontiers in Immunology
adenosquamous lung carcinoma (ASLC)
adenocarcinoma-to-squamous cell carcinoma transformation (AST)
tumor immune microenvironment (TIME)
tumor-associated macrophages (TAMs)
tumor-associated neutrophils (TANs)
title Unraveling the immune mechanisms and therapeutic targets in lung adenosquamous transformation
title_full Unraveling the immune mechanisms and therapeutic targets in lung adenosquamous transformation
title_fullStr Unraveling the immune mechanisms and therapeutic targets in lung adenosquamous transformation
title_full_unstemmed Unraveling the immune mechanisms and therapeutic targets in lung adenosquamous transformation
title_short Unraveling the immune mechanisms and therapeutic targets in lung adenosquamous transformation
title_sort unraveling the immune mechanisms and therapeutic targets in lung adenosquamous transformation
topic adenosquamous lung carcinoma (ASLC)
adenocarcinoma-to-squamous cell carcinoma transformation (AST)
tumor immune microenvironment (TIME)
tumor-associated macrophages (TAMs)
tumor-associated neutrophils (TANs)
url https://www.frontiersin.org/articles/10.3389/fimmu.2025.1542526/full
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