Distinct immune microenvironment of lung adenocarcinoma in never-smokers from smokers

Luo, Wenxin; Zeng, Zhen; Jiang, Yang; Yang, Lei; Fan, Ting; Wang, Zhoufeng; Pan, Yuning; Yang, Ying; Yao, Menglin; Li, Yangqian; Xiao, Xu; Wang, Gang; Wang, Chengdi; Chang, Shuai; Che, Guowei; Zhang, Li; Li, Yalun; Peng, Yong; Liu, Weimin

doi:10.1016/j.xcrm.2023.101078

Cited by 18 publications

(7 citation statements)

References 61 publications

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“…5). We speculated that the modifying effects of smoking status could be partly due to the distinct immune microenvironment between smokers, secondhand smokers and non-smokers [71]. However, it should be noted that despite our efforts to adjust for available co-variates in the models, the existence of residual confounding could not be totally eliminated in the subgroup analyses.…”

Section: Discussionmentioning

confidence: 98%

Association between metal exposures and periodontitis among U.S. adults: the potential mediating role of biological aging

Dai,

Fu,

Tan

et al. 2024

Environ Sci Eur

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Background This study aimed to investigate the associations between metal exposures and periodontitis among U.S. adults, as well as the mediated effect of biological aging. Methods Using data from the National Health and Nutrition Examination Survey (NHANES) 2009–2014, we explored the single and mixed impacts of metal exposures on periodontitis through adjusted weighted logistic regression, robust Poisson regression, restricted cubic spline regression, and Bayesian kernel machine regression models. This study included 2,393 participants, with 46.9% experiencing periodontitis. Concentrations of nine urinary metals, including barium (Ba), cadmium (Cd), cobalt (Co), cesium (Cs), molybdenum (Mo), lead (Pb), thallium (Tl), tungsten (Tu), and uranium (Ur), were measured using inductively coupled plasma-mass spectrometry. In addition, we analyzed the association between metals and periodontitis, stratified by age, body mass index, gender, and smoking status. Mediation models were also applied to investigate the mediated effects of biological aging between metal exposures and periodontitis. Results Weighted logistic and robust Poisson regression identified positive associations between Cd, Pb and periodontitis (P < 0.05). BKMR analyses indicated that mixed metal exposures were significantly associated with periodontitis, particularly among smokers, second-hand smokers, and males, with Cd, Pb, Tl, and Ba contributing the most. Furthermore, subgroup analyses observed a modifying effect on the associations between urinary Cd, Pb and periodontitis in stratified gender and BMI subgroups in robust Poisson regression. Phenotype age was found to mediate the association between metals and periodontitis. Conclusions This study identified significant positive associations between metal exposures and periodontitis in the U.S. adults. In addition, the association between metal exposures and periodontitis could vary in different gender, BMI and smoking subgroups. These associations were likely partly mediated by biological aging, suggesting that metals may potentially increase the risk of periodontitis by promoting cell senescence and overall aging of the body. Graphical Abstract

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Section: Discussionmentioning

confidence: 98%

Association between metal exposures and periodontitis among U.S. adults: the potential mediating role of biological aging

Dai,

Fu,

Tan

et al. 2024

Environ Sci Eur

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“…The present study suggests that COPD can significantly affect the efficacy of neoadjuvant immunotherapy. One explanation may be that COPD alters the immune microenvironment of tumors independent of smoking, which may also affect the immune microenvironment [ 13 , 23 ]. Previous studies have shown an increase in T-helper cell type 1 (Th1) differentiation of lymphocytes within the tumor microenvironment of NSCLC patients with COPD [ 13 , 24 ].…”

Section: Discussionmentioning

confidence: 99%

Impact of chronic obstructive pulmonary disease on the efficacy and safety of neoadjuvant immune checkpoint inhibitors combined with chemotherapy for resectable non-small cell lung cancer: a retrospective cohort study

Dong,

Yin,

Yang

et al. 2024

BMC Cancer

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Background Neoadjuvant immune checkpoint inhibitors(ICIs) combined with chemotherapy can improve non-small cell lung cancer(NSCLC) patients' pathological responses and show promising improvements in survival. Chronic obstructive pulmonary disease (COPD) is a systemic inflammatory disease, and its associated abnormal inflammatory response affects not only the immunotherapy efficacy but also immune-related adverse events. It remains unclear whether NSCLC patients with COPD can benefit from neoadjuvant ICIs combined with chemotherapy. Methods A retrospective observational clinical study was conducted on 105 consecutive NSCLC patients receiving neoadjuvant ICIs combined with chemotherapy at the Department of Thoracic Surgery of Tianjin Chest Hospital between April 2020 and April 2023. Results A total of 74 NSCLC patients were included in the study, including 30 patients with COPD and 44 patients without COPD. The percentage of patients with a pathological complete response (PCR) was higher in the COPD group than in the non-COPD group (43.3% vs. 20.5%, P = 0.042). Multivariate logistic regression analysis of factors associated with PCR showed that the adjusted odds ratio (OR) was statistically significant for presence of COPD (OR = 3.020, 95%CI: 1.042–8.757; P = 0.042). Major pathological response (66.7% vs. 50%, P = 0.155), R0 resection rate (96.7% vs.93.2%, P = 0.642), N2 lymph node downstaging(92.3% vs. 66.7%, P = 0.182) and objective response rate (70% vs. 63.6%, P = 0.57) were not significantly different between the groups. Progression-free survival(PFS) was not reached in the COPD group and 17 months (95%CI: 12.1–21.9) in the non-COPD group, with statistically significance (χ2 = 6.247, P = 0.012). Multivariate Cox’s regression analysis showed that the adjusted hazard ratio (HRadj) was statistically significant for presence of COPD (HRadj = 0.321, 95%CI: 0.111–0.930; P = 0.036). The grade 3 and grade 4 adverse events in the COPD group were leukopenia (3.3%, 6.7%), neutropenia (3.3%, 6.7%), fatigue (6.7%, 0%), gastrointestinal reactions (3.3%, 0%), and hypothyroidism (3.3%, 0%). In the non-COPD group, the corresponding adverse events were leukopenia (6.8%, 6.8%), neutropenia (3.3%, 6.8%), fatigue (2.3%, 0%), gastrointestinal reactions (2.3%, 0%), and hypothyroidism (2.3%, 0%), respectively. Conclusions The present study indicates that the presence of COPD may improve PCR, prolong PFS, and have an acceptable safety profile in NSCLC patients receiving neoadjuvant ICIs combined with chemotherapy.

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“…The effective distinction of molecular and immunologic phenotypes in the early-stage of LUAD can guide the use of targeted therapy or immunotherapies. Studies now suggest that AT2 cells are the genetic origin of lung adenocarcinoma [ 77 ], hence SP-C is strongly enriched in lung cancer tissue. Additionally, research has also indicated the activation of adaptive immune responses during the progression of LUAD, manifested by the gradual enrichment of T cells and B cells, and a decrease in NK cells and granulocytes [ 78 ].…”

Section: Discussionmentioning

confidence: 99%

Novel genome-wide DNA methylation profiling reveals distinct epigenetic landscape, prognostic model and cellular composition of early-stage lung adenocarcinoma

Gan,

Huang,

Wang

et al. 2024

J Transl Med

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Background Lung adenocarcinoma (LUAD) has been a leading cause of cancer-related mortality worldwide. Early intervention can significantly improve prognosis. DNA methylation could occur in the early stage of tumor. Comprehensive understanding the epigenetic landscape of early-stage LUAD is crucial in understanding tumorigenesis. Methods Enzymatic methyl sequencing (EM-seq) was performed on 23 tumors and paired normal tissue to reveal distinct epigenetic landscape, for compared with The Cancer Genome Atlas (TCGA) 450K methylation microarray data. Then, an integrative analysis was performed combined with TCGA LUAD RNA-seq data to identify significant differential methylated and expressed genes. Subsequently, the prognostic risk model was constructed and cellular composition was analyzed. Results Methylome analysis of EM-seq comparing tumor and normal tissues identified 25 million cytosine-phosphate-guanine (CpG) sites and 30,187 differentially methylated regions (DMR) with a greater number of untraditional types. EM-seq identified a significantly higher number of CpG sites and DMRs compared to the 450K microarray. By integrating the differentially methylated genes (DMGs) with LUAD-related differentially expressed genes (DEGs) from the TCGA database, we constructed prognostic model based on six differentially methylated-expressed genes (MEGs) and verified our prognostic model in GSE13213 and GSE42127 dataset. Finally, cell deconvolution based on the in-house EM-seq methylation profile was used to estimate cellular composition of early-stage LUAD. Conclusions This study firstly delves into novel pattern of epigenomic DNA methylation and provides a multidimensional analysis of the role of DNA methylation revealed by EM-seq in early-stage LUAD, providing distinctive insights into its potential epigenetic mechanisms.

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Distinct immune microenvironment of lung adenocarcinoma in never-smokers from smokers

Cited by 18 publications

References 61 publications

Association between metal exposures and periodontitis among U.S. adults: the potential mediating role of biological aging

Association between metal exposures and periodontitis among U.S. adults: the potential mediating role of biological aging

Impact of chronic obstructive pulmonary disease on the efficacy and safety of neoadjuvant immune checkpoint inhibitors combined with chemotherapy for resectable non-small cell lung cancer: a retrospective cohort study

Novel genome-wide DNA methylation profiling reveals distinct epigenetic landscape, prognostic model and cellular composition of early-stage lung adenocarcinoma

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