Distinctive Regulatory T Cells and Altered Cytokine Profile Locally in the Airways of Young Smokers with Normal Lung Function

Ostadkarampour, Mahyar; Müller, Malin; Öckinger, Johan; Kullberg, Susanna; Lindén, Anders; Eklúnd, Anders; Grünewald, Johan; Wahlström, Jan

doi:10.1371/journal.pone.0164751

Cited by 2 publications

(1 citation statement)

References 38 publications

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“…Ostadkarampour et al have reported an increased frequency of a potent suppressor Treg subset and a decreased frequency of Th17 cells in the BAL of young healthy moderate smokers with normal lung function, relative to healthy never-smokers. 39 Chronic obstructive pulmonary disease (COPD) is a lung disorder highly associated with cigarette smoking. About 90% of COPD patients are current smokers or exsmokers, and about 50% of lifelong smokers develop COPD.…”

Section: Cigarette Smokingmentioning

confidence: 99%

<p>“High Treg” Inflammations Promote (Most) Non-Hematologic Cancers While “Low Treg” Inflammations Promote Lymphoid Cancers</p>

Elkoshi¹

2020

JIR

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In an earlier publication, a binary classification of chronic diseases has been proposed. Chronic diseases were classified as "high Treg" or "low Treg" diseases depending on whether the pro-inflammatory or the anti-inflammatory arms of the immune response are deficient. The present work uses this model to analyze the interplay between cancer and the immune system, based on published literature. The work leans upon the etiology of alcohol and tobacco-related malignancies. The main conclusions are: triggers of specific "high Treg" immune reaction promote most non-hematologic cancers, whereas triggers of "low Treg" immune reaction promote lymphomas. The opposite is also true: triggers of specific "high Treg" immune reaction suppress lymphoma, whereas triggers of "low Treg" immune reaction suppress non-hematologic cancers. Both lymphoma and autoimmune diseases are "low Treg" conditions. For this reason, both are promoted by the same panel of "low Treg" bacteria and parasites and are inhibited by "high Treg" triggers. For example, alcohol consumption, a "high Treg" trigger, protects against lymphoma and autoimmune hypothyroidism. In addition, the same immune-modulatory drugs are effective in the treatment of both lymphoma and autoimmune diseases. Like other cancers, lymphoma transforms from a "low Treg" type at early stage of the disease into a "high Treg" type at advanced stages. However, lymphoma is distinguished from most other cancers by the length of time it dwells at an indolent "low Treg" state (many years) before lymphoma cells sensitivity to transforming growth factor-beta is impaired. This impairment stimulates the switch from "low Treg" into "high Treg" response and results in immune escape. The application of this analysis to the pharmacological activity of checkpoint inhibitors forecasts that checkpoint inhibitors would not be effective in low-grade, indolent lymphomas. As of now, checkpoint inhibitors are approved for the treatment of advanced lymphoma only.

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Section: Cigarette Smokingmentioning

confidence: 99%

<p>“High Treg” Inflammations Promote (Most) Non-Hematologic Cancers While “Low Treg” Inflammations Promote Lymphoid Cancers</p>

Elkoshi¹

2020

JIR

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Lifetime Exposure to Cigarette Smoke and Risk of Ovarian Cancer by T-cell Tumor Immune Infiltration

Hathaway

Wang

Townsend

et al. 2022

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Background: Exposure to cigarette smoke, particularly in early life, is modestly associated with ovarian cancer risk and may impact systemic immunity and the tumor immune response. However, no studies have evaluated whether cigarette smoke exposure impacts the ovarian tumor immune microenvironment. Methods: Participants in the Nurses’ Health Study (NHS) and NHSII reported on early life exposure to cigarette smoke and personal smoking history on questionnaires (n=165,760). Multiplex immunofluorescence assays were used to measure markers of T cells and immune checkpoints in tumor tissue from 385 incident ovarian cancer cases. We used Cox proportional hazards models to evaluate hazard ratios (HR) and 95% confidence intervals (CI) for developing ovarian tumors with a low (<median) or high (≥median) immune cell percentage by cigarette exposure categories. Results: Women exposed versus not to cigarette smoke early in life had a higher risk of developing ovarian cancer with low levels of T cells overall (CD3+: HR: 1.54, 95%CI: 1.08, 2.20) and recently activated cytotoxic T cells (CD3+CD8+CD69+: HR: 1.45, 95%CI: 1.05, 2.00). These findings were not statistically significant at the Bonferroni corrected p-value of 0.0083. Adult smoking was not significantly associated with tumor immune markers after Bonferroni correction. Conclusion: These results suggest early life cigarette smoke exposure may modestly increase risk of developing ovarian tumors with low abundance of total T cells and recently activated cytotoxic T cells. Impact: Future research should focus on understanding the impact of exposures throughout the life course on the ovarian tumor immune microenvironment.

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Distinctive Regulatory T Cells and Altered Cytokine Profile Locally in the Airways of Young Smokers with Normal Lung Function

Cited by 2 publications

References 38 publications

<p>“High Treg” Inflammations Promote (Most) Non-Hematologic Cancers While “Low Treg” Inflammations Promote Lymphoid Cancers</p>

<p>“High Treg” Inflammations Promote (Most) Non-Hematologic Cancers While “Low Treg” Inflammations Promote Lymphoid Cancers</p>

Lifetime Exposure to Cigarette Smoke and Risk of Ovarian Cancer by T-cell Tumor Immune Infiltration

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