Implications of the Immune Landscape in COPD and Lung Cancer: Smoking Versus Other Causes

Taucher, Elisabeth; Mykoliuk, Iurii; Lindenmann, Joerg; Smolle‐Juettner, Freyja‐Maria

doi:10.3389/fimmu.2022.846605

Cited by 32 publications

(17 citation statements)

References 246 publications

(282 reference statements)

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“…The self-perpetuating systemic inflammation caused by tobacco smoking has been intensively studied earlier by our group and others (5,43,44). Cigarette smoking caused alterations in the peripheral immune landscape in COPD that has been reviewed by Taucher et al (45). Using single-cell mass cytometry, we have recently shown the peripheral immunophenotype of smoker advanced NSCLC patients who underwent chemotherapy or immune checkpoint inhibitor (ICI) therapy (34).…”

Section: Discussionmentioning

confidence: 93%

Single-cell immunophenotyping revealed the association of CD4+ central and CD4+ effector memory T cells linking exacerbating chronic obstructive pulmonary disease and NSCLC

Gémes,

Balog,

Neuperger

et al. 2023

Front. Immunol.

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IntroductionTobacco smoking generates airway inflammation in chronic obstructive pulmonary disease (COPD), and its involvement in the development of lung cancer is still among the leading causes of early death. Therefore, we aimed to have a better understanding of the disbalance in immunoregulation in chronic inflammatory conditions in smoker subjects with stable COPD (stCOPD), exacerbating COPD (exCOPD), or non-small cell lung cancer (NSCLC).MethodsSmoker controls without chronic illness were recruited as controls. Through extensive mapping of single cells, surface receptor quantification was achieved by single-cell mass cytometry (CyTOF) with 29 antibodies. The CyTOF characterized 14 main immune subsets such as CD4+, CD8+, CD4+/CD8+, CD4−/CD8−, and γ/δ T cells and other subsets such as CD4+ or CD8+ NKT cells, NK cells, B cells, plasmablasts, monocytes, CD11cdim, mDCs, and pDCs. The CD4+ central memory (CM) T cells (CD4+/CD45RA−/CD45RO+/CD197+) and CD4+ effector memory (EM) T cells (CD4+/CD45RA−/CD45RO+/CD197−) were FACS-sorted for RNA-Seq analysis. Plasma samples were assayed by Luminex MAGPIX® for the quantitative measurement of 17 soluble immuno-oncology mediators (BTLA, CD28, CD80, CD27, CD40, CD86, CTLA-4, GITR, GITRL, HVEM, ICOS, LAG-3, PD-1, PD-L1, PD-L2, TIM-3, TLR-2) in the four studied groups.ResultsOur focus was on T-cell-dependent differences in COPD and NSCLC, where peripheral CD4+ central memory and CD4+ effector memory cells showed a significant reduction in exCOPD and CD4+ CM showed elevation in NSCLC. The transcriptome analysis delineated a perfect correlation of differentially expressed genes between exacerbating COPD and NSCLC-derived peripheral CD4+ CM or CD4+ EM cells. The measurement of 17 immuno-oncology soluble mediators revealed a disease-associated phenotype in the peripheral blood of stCOPD, exCOPD, and NSCLC patients.DiscussionThe applied single-cell mass cytometry, the whole transcriptome profiling of peripheral CD4+ memory cells, and the quantification of 17 plasma mediators provided complex data that may contribute to the understanding of the disbalance in immune homeostasis generated or sustained by tobacco smoking in COPD and NSCLC.

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Section: Discussionmentioning

confidence: 93%

Single-cell immunophenotyping revealed the association of CD4+ central and CD4+ effector memory T cells linking exacerbating chronic obstructive pulmonary disease and NSCLC

Gémes,

Balog,

Neuperger

et al. 2023

Front. Immunol.

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“…Compared to non-smokers, former and current smokers were found to be more likely to suffer from multimorbidity using global regression and GWLR model. Studies have proven that tobacco contains various toxic and carcinogenic compounds that can lead to various diseases, including cardiovascular, cancer, respiratory, and neurological diseases [ 23 ]. For example, in a population-based biomedical cohort study in Australia, current smokers were 1.71 times more likely to develop multimorbidity than non-smokers [ 24 ].…”

Section: Discussionmentioning

confidence: 99%

Geographical specific association between lifestyles and multimorbidity among adults in China

et al. 2023

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The relationship between lifestyles and multimorbidity is well established, but previous studies have often neglected the role of spatial heterogeneity. Thus, this study is the first to explore this association in Chinese adults from a spatial perspective using a geographically weighted logistic regression (GWLR) model and describe the geographical characteristics across different regions. According to 2018 China Health and Retirement Longitudinal Study (CHARLS) database, a total of 7101 subjects were finally included, with 124 prefecture-level administrative regions in China. Non-spatial and GWLR model were used for analysis, and gender stratification analysis was also performed. Data were visualized through ArcGIS 10.7. The results showed that a total prevalence of approximately 5.13% of multimorbidity, and among participants with multimorbidity, the separate prevalence of hypertension, diabetes or high blood sugar, heart disease, and stroke were 4.45%, 2.32%, 3.02%, and 1.41%, respectively. The GWLR model indicated that current (OR: 1.202–1.220) and former smokers (OR: 1.168–1.206) may be important risk factors for multimorbidity in adults, especially in north and west among male. Past drinkers (OR: 1.233–1.240), especially in eastern China, contribute to the development of the multimorbidity in men but not in women. Vigorous-intensity activities (OR: 0.761–0.799) were negatively associated with multimorbidity in the west, with no gender difference. Depression (OR: 1.266–1.293) appeared to increase the risk for multimorbidity, with the weakest effects in central China and no gender difference. There was an interaction between light activities and gender (P = 0.024). The prevalence of multimorbidity differed across various areas of the province. The role of geographical variations in lifestyles and multimorbidity may provide valuable information for developing site-specific intervention strategies.

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“…Literature highlight that numerous carcinogens plays a key role in lung carcinogenesis and major components are identified in the cigarette smoke. [ 4 ]…”

Section: Introductionmentioning

confidence: 99%

“…Literature highlight that numerous carcinogens plays a key role in lung carcinogenesis and major components are identified in the cigarette smoke. [4] Benzo (a) pyrene (B(a)P), a strong carcinogen is abundant in tobacco smoke. B(a)P is grouped under polycyclic aromatic hydrocarbons.…”

mentioning

confidence: 99%

Immunomodulatory effect of Myrtenol on benzo (a) pyrene‐induced lung cancer in Swiss albino mice via modulation of tumor markers, cytokines and inhibition of PCNA expression

Zhang,

Ramamoorthy,

Rengarajan

et al. 2023

J Biochem & Molecular Tox

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Lung cancer is one of the most common cancers in men. Although many diagnostic and treatment regimens have been followed in the treatment for lung cancer, increasing mortality rate due to lung cancer is depressing and hence requires alternative plant based therapeutics with with less side‐effects. Myrtenol exhibits anti‐inflammatory and antioxidant properties. Hence we intended to study the effect of Myrtenol on B(a)P‐induced lung cancer. Our study showed that B(a)P lowered hematological count, decreased phagocyte and avidity indices, nitroblue tetrazolium (NBT) reduction, levels of immunoglubulins, antioxidant levels, whereas Myrtenol treatment restored them back to normal levels. On the other hand, xenobiotic and liver dysfunction marker enzymes and pro‐inflammatory cytokines were elevated on B(a)P exposure, which retuned back to normal by Myrtenol. This study thus describes the immunomodulatory and antioxidant effects of Myrtenol on B[a]P‐induced immune destruction.

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Implications of the Immune Landscape in COPD and Lung Cancer: Smoking Versus Other Causes

Cited by 32 publications

References 246 publications

Single-cell immunophenotyping revealed the association of CD4+ central and CD4+ effector memory T cells linking exacerbating chronic obstructive pulmonary disease and NSCLC

Single-cell immunophenotyping revealed the association of CD4+ central and CD4+ effector memory T cells linking exacerbating chronic obstructive pulmonary disease and NSCLC

Geographical specific association between lifestyles and multimorbidity among adults in China

Immunomodulatory effect of Myrtenol on benzo (a) pyrene‐induced lung cancer in Swiss albino mice via modulation of tumor markers, cytokines and inhibition of PCNA expression

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