Nicotine and tar-multiple targets synergize to alter the immune micro-environment to induce prostate cancer

Abstract Background Prostate cancer (PC) is a common urinary system malignancy in men, and smoking is a clear risk factor. Among them, nicotine and tar in cigarettes play a key role in the development of PC, but the specific mechanism is not completely clear. Objective To explore the mechanism of PC...

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Main Authors: Lianlin Zeng, Yajie He, Fei Huang, Xiaoqian Jiang, Yang-An Li, Kehui Hu
Format: Article
Language:English
Published: Springer 2025-07-01
Series:Discover Oncology
Subjects:
Online Access:https://doi.org/10.1007/s12672-025-03137-3
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author Lianlin Zeng
Yajie He
Fei Huang
Xiaoqian Jiang
Yang-An Li
Kehui Hu
author_facet Lianlin Zeng
Yajie He
Fei Huang
Xiaoqian Jiang
Yang-An Li
Kehui Hu
author_sort Lianlin Zeng
collection DOAJ
description Abstract Background Prostate cancer (PC) is a common urinary system malignancy in men, and smoking is a clear risk factor. Among them, nicotine and tar in cigarettes play a key role in the development of PC, but the specific mechanism is not completely clear. Objective To explore the mechanism of PC immune inflammation caused by nicotine and tar, and to provide the theoretical basis and new targets for the prevention and treatment of PC. Methods Through network toxicology and immune infiltration analysis, to analyze the effects of nicotine and tar on PC related cells and tissues, and machine analysis of related cytokines, signaling pathway and gene expression changes. Key genes were validated by immunohistochemistry and in vitro cellular assays. Results This study screened multiple targets of nicotine and tar that may be related to the occurrence of PC. In addition, based on these targets and signaling pathways, they may be key molecular mechanisms leading to PC. In the formation and progression of PC, we found significant infiltration of M2 macrophages, with increased secretion of VEGF, MMPs, IL-10, etc., promoting tumor angiogenesis, extracellular matrix degradation, and leading to immune escape in the body. Inhibition of T cell activity, macrophages interact with tumor cells, smooth muscle cells, affect each other’s functions. Functional of CD8 + T cells, tumor cells promote immune escape by binding of PD-L1 and PD-1. Hub targets such as MAOA and MAOB are affected by nicotine and tar, interference with neurotransmitters, hormones, lipid metabolism, activation of the inflammatory signals, altering the immune microenvironment, to promote the development and development of PC. Conclusion Nicotine and tar may contribute to the development of PC through complex immuno-inflammatory mechanisms, and in-depth study of these mechanisms could help develop more effective prevention and treatment strategies for PC.
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spelling doaj-art-8e5824ac36b64e27878a7f681edfb6072025-08-20T03:42:57ZengSpringerDiscover Oncology2730-60112025-07-0116112210.1007/s12672-025-03137-3Nicotine and tar-multiple targets synergize to alter the immune micro-environment to induce prostate cancerLianlin Zeng0Yajie He1Fei Huang2Xiaoqian Jiang3Yang-An Li4Kehui Hu5Department of Rehabilitation, Suining Central HospitalDepartment of Pathology, Suining Central HospitalDepartment of Rehabilitation, Suining Central HospitalDepartment of Rehabilitation, Suining Central HospitalDepartment of Rehabilitation, Suining Central HospitalDepartment of Rehabilitation, Suining Central HospitalAbstract Background Prostate cancer (PC) is a common urinary system malignancy in men, and smoking is a clear risk factor. Among them, nicotine and tar in cigarettes play a key role in the development of PC, but the specific mechanism is not completely clear. Objective To explore the mechanism of PC immune inflammation caused by nicotine and tar, and to provide the theoretical basis and new targets for the prevention and treatment of PC. Methods Through network toxicology and immune infiltration analysis, to analyze the effects of nicotine and tar on PC related cells and tissues, and machine analysis of related cytokines, signaling pathway and gene expression changes. Key genes were validated by immunohistochemistry and in vitro cellular assays. Results This study screened multiple targets of nicotine and tar that may be related to the occurrence of PC. In addition, based on these targets and signaling pathways, they may be key molecular mechanisms leading to PC. In the formation and progression of PC, we found significant infiltration of M2 macrophages, with increased secretion of VEGF, MMPs, IL-10, etc., promoting tumor angiogenesis, extracellular matrix degradation, and leading to immune escape in the body. Inhibition of T cell activity, macrophages interact with tumor cells, smooth muscle cells, affect each other’s functions. Functional of CD8 + T cells, tumor cells promote immune escape by binding of PD-L1 and PD-1. Hub targets such as MAOA and MAOB are affected by nicotine and tar, interference with neurotransmitters, hormones, lipid metabolism, activation of the inflammatory signals, altering the immune microenvironment, to promote the development and development of PC. Conclusion Nicotine and tar may contribute to the development of PC through complex immuno-inflammatory mechanisms, and in-depth study of these mechanisms could help develop more effective prevention and treatment strategies for PC.https://doi.org/10.1007/s12672-025-03137-3Prostate cancerNetwork toxicologyImmune infiltrationNicotine and tar
spellingShingle Lianlin Zeng
Yajie He
Fei Huang
Xiaoqian Jiang
Yang-An Li
Kehui Hu
Nicotine and tar-multiple targets synergize to alter the immune micro-environment to induce prostate cancer
Discover Oncology
Prostate cancer
Network toxicology
Immune infiltration
Nicotine and tar
title Nicotine and tar-multiple targets synergize to alter the immune micro-environment to induce prostate cancer
title_full Nicotine and tar-multiple targets synergize to alter the immune micro-environment to induce prostate cancer
title_fullStr Nicotine and tar-multiple targets synergize to alter the immune micro-environment to induce prostate cancer
title_full_unstemmed Nicotine and tar-multiple targets synergize to alter the immune micro-environment to induce prostate cancer
title_short Nicotine and tar-multiple targets synergize to alter the immune micro-environment to induce prostate cancer
title_sort nicotine and tar multiple targets synergize to alter the immune micro environment to induce prostate cancer
topic Prostate cancer
Network toxicology
Immune infiltration
Nicotine and tar
url https://doi.org/10.1007/s12672-025-03137-3
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