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Lu X, Ma L, Yin X, et al. The impact of tobacco exposure on tumor microenvironment and prognosis in lung adenocarcinoma by integrative analysis of multi-omics data. Int Immunopharmacol. 2021;101:108253doi: 10.1016/j.intimp.2021.108253.
Lu, X., Ma, L., Yin, X., Ji, H., Qian, Y., Zhong, S., Yan, A., & Zhang, Y. (2021). The impact of tobacco exposure on tumor microenvironment and prognosis in lung adenocarcinoma by integrative analysis of multi-omics data. International immunopharmacology, 101108253. https://doi.org/10.1016/j.intimp.2021.108253
Lu, Xiaomin, et al. "The impact of tobacco exposure on tumor microenvironment and prognosis in lung adenocarcinoma by integrative analysis of multi-omics data." International immunopharmacology vol. 101 (2021): 108253. doi: https://doi.org/10.1016/j.intimp.2021.108253
Lu X, Ma L, Yin X, Ji H, Qian Y, Zhong S, Yan A, Zhang Y. The impact of tobacco exposure on tumor microenvironment and prognosis in lung adenocarcinoma by integrative analysis of multi-omics data. Int Immunopharmacol. 2021 Dec;101:108253. doi: 10.1016/j.intimp.2021.108253. Epub 2021 Oct 23. PMID: 34700112.
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Int Immunopharmacol. 2021 Dec;101:108253. doi: 10.1016/j.intimp.2021.108253. Epub 2021 Oct 23.

The impact of tobacco exposure on tumor microenvironment and prognosis in lung adenocarcinoma by integrative analysis of multi-omics data.

International immunopharmacology

Xiaomin Lu, Liang Ma, Xuewen Yin, Haoming Ji, Ye Qian, Sixun Zhong, Aiting Yan, Yan Zhang

Affiliations

  1. Department of Oncology, Affiliated Haian Hospital of Nantong University, Haian Town, Haian County, Nantong, Jiangsu 226601, China. Electronic address: [email protected].
  2. Department of Oncology, The Forth Affiliated Hospital of Nantong University, The First People's Hospital of Yancheng, Yancheng, Jiangsu, China.
  3. Department of Clinical Pharmacy, School of Basic Medical Sciences and Clinical Pharmacy, China Pharmaceutical University, Nanjing 210009, China.
  4. Department of Oncology, Affiliated Haian Hospital of Nantong University, Haian Town, Haian County, Nantong, Jiangsu 226601, China.
  5. Department of Oncology, Affiliated Haian Hospital of Nantong University, Haian Town, Haian County, Nantong, Jiangsu 226601, China. Electronic address: [email protected].

PMID: 34700112 DOI: 10.1016/j.intimp.2021.108253

Abstract

BACKGROUND: Immune checkpoint inhibitors (ICIs) are standard therapies for patients with advanced lung adenocarcinoma and significantly improve treatment outcomes. The effect of tobacco smoking on the response of immune checkpoint inhibitors is somewhat diverging. Here, we assessed the impact of tobacco exposure on the tumor microenvironment and developed a feasible tool for predicting prognosis.

METHODS: Whole exon sequence data and the corresponding clinical information were downloaded from the Cancer Genome Atlas. The signature was developed by the Random Forest algorithm. CIBERSORTx online tool was used to estimate immune infiltration. Functional assays were performed to assess the roles of tobacco exposure in cancer cells. Immunohistochemistry (IHC) was performed to identify and validate the immune activation status.

RESULTS: The TMB of lifelong non-smoker, current reformed smoker for over 15 years, current reformed smoker<15 years and current smoker had a significantly increasing trend in LUAD patients. In vitro tobacco exposure promoted the expression of PD-L1 and malignant phenotype of LUAD cells. In addition, patients with high Random Forest score (RFscore) had a poorer prognosis than those with low RFscore. The ROC curve analysis of RFscore revealed a promising prognostic capability. Memory activated CD4 + T cells, CD8 + t cells and memory B cells were noticeably enriched in the high RFscore group and PDCD1 appreciably upregulated in the high RFscore group as well. Furthermore, IHC results suggested that patients with high RFscore remained an immune activation status, indicating a positive correlation between RFscore and patient's immune status.

CONCLUSION: Our analysis provides further insight into the profound impacts of tobacco exposure on tumor immune microenvironment and envisions integrative predictive models of RFscore, predicting the prognosis of smoking lung adenocarcinoma, which might help to understand the potential mechanism of smoking exposure on tumor immune microenvironment.

Copyright © 2021 Elsevier B.V. All rights reserved.

Keywords: Immune status; Immunotherapy; Lung cancer; Microenvironment; RFscore

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