HLA-C and KIR permutations influence chronic obstructive pulmonary disease risk

Mkorombindo, Takudzwa; Tran-Nguyen, Thi K.; Yuan, Kaiyu; Zhang, Yingze; Xue, Jun; Criner, Gerard J.; Kim, Young-il; Pilewski, Joseph M.; Gaggar, Amit; Cho, Michael H.; Sciurba, Frank C.; Duncan, Steven R.

doi:10.1172/jci.insight.150187

Cited by 6 publications

(5 citation statements)

References 46 publications

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“…In line with this evidence and as NSCLC might block the expression of HLA class I molecules to escape immune surveillance, potential immunomodulatory and MHCencoding genes overexpressed in NSCLC and COPD have been studied as promising biomarkers of responses to immunotherapy [113][114][115][116][117][118].…”

Section: Other Predictive Biomarkers Evaluated In Nsclc Patients With...mentioning

confidence: 87%

Effectiveness of Immunotherapy in Non-Small Cell Lung Cancer Patients with a Diagnosis of COPD: Is This a Hidden Prognosticator for Survival and a Risk Factor for Immune-Related Adverse Events?

Riondino,

Rosenfeld,

Formica

et al. 2024

Cancers

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The interplay between the immune system and chronic obstructive pulmonary disease (COPD) and non-small cell lung cancer (NSCLC) is complex and multifaceted. In COPD, chronic inflammation and oxidative stress can lead to immune dysfunction that can exacerbate lung damage, further worsening the respiratory symptoms. In NSCLC, immune cells can recognise and attack the cancer cells, which, however, can evade or suppress the immune response by various mechanisms, such as expressing immune checkpoint proteins or secreting immunosuppressive cytokines, thus creating an immunosuppressive tumour microenvironment that promotes cancer progression and metastasis. The interaction between COPD and NSCLC further complicates the immune response. In patients with both diseases, COPD can impair the immune response against cancer cells by reducing or suppressing the activity of immune cells, or altering their cytokine profile. Moreover, anti-cancer treatments can also affect the immune system and worsen COPD symptoms by causing lung inflammation and fibrosis. Immunotherapy itself can also cause immune-related adverse events that could worsen the respiratory symptoms in patients with COPD-compromised lungs. In the present review, we tried to understand the interplay between the two pathologies and how the efficacy of immunotherapy in NSCLC patients with COPD is affected in these patients.

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Section: Other Predictive Biomarkers Evaluated In Nsclc Patients With...mentioning

confidence: 87%

Effectiveness of Immunotherapy in Non-Small Cell Lung Cancer Patients with a Diagnosis of COPD: Is This a Hidden Prognosticator for Survival and a Risk Factor for Immune-Related Adverse Events?

Riondino,

Rosenfeld,

Formica

et al. 2024

Cancers

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show abstract

“…HLA-C is one of the major genes associated with autoimmune diseases [19]. Previously this has also been found to be associated with COPD [20]. Surfactant protein D (SFTPD) is a lung-specific protein and has been found in COPD GWAS studies [21].…”

Section: Discussionmentioning

confidence: 99%

Chronic Obstructive Pulmonary Disease (COPD): Making Sense of Existing GWAS Findings in Indian Context

Dutta,

Bhattacharya

2022

Int J Biomed Clin Anal

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To date, more than 1456 associations have been identified for Chronic Obstructive Pulmonary Disease (COPD) risk through Genome-Wide Association Studies (GWAS). However, target genes for COPD susceptibility in the Indian population and the mechanism underlying remains largely unexplored and no GWAS studies on COPD are available on the Indian population till now. This study was conducted using the existing public data on GWAS of different parts of the world, and the genetic polymorphisms to understand the possible mechanisms of these polymorphisms using available data from the Genotype-Tissue Expression (GTEx) project. We jotted down 16 important genes and 28 Single Nucleotide Polymorphisms (SNPs) in the Indian population from 1456 variants. Pathway analysis showed that these relevant genes are mostly associated with immune responses and activation, which is a key factor in COPD development. Our investigation revealed possible target genes associated with COPD in the context of the Indian population.

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“…Within the scope of the HLA system, multiple studies have elucidated intricate interactions between certain HLA alleles, like HLA-DR, and cigarette smoking, especially in autoimmune disorders akin to rheumatoid arthritis [72,73]. Notably, HLA-B and HLA-C are linked to smokingassociated ailments, including COPD and lung cancer [74,75]. A particular study revealed that MHC-I molecules, encompassing HLA-B and HLA-C, exhibited reduced expression in lung adenocarcinoma patients who were non-smokers compared to those who smoked [76].…”

Section: Qualitative Features In Lung Immune Cellsmentioning

confidence: 99%

Machine Learning Reveals Impacts of Smoking on Gene Profiles of Different Cell Types in Lung

Ma,

Shen,

Guo

et al. 2024

Life

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Smoking significantly elevates the risk of lung diseases such as chronic obstructive pulmonary disease (COPD) and lung cancer. This risk is attributed to the harmful chemicals in tobacco smoke that damage lung tissue and impair lung function. Current research on the impact of smoking on gene expression in specific lung cells is limited. This study addresses this gap by analyzing gene expression profiles at the single-cell level from 43,539 lung endothelial cells, 234,349 lung epithelial cells, 189,843 lung immune cells, and 16,031 lung stromal cells using advanced machine learning techniques. The data, categorized by different lung cell types, were classified into three smoking states: active smoker, former smoker, and never smoker. Each cell sample encompassed 28,024 feature genes. Employing an incremental feature selection method within a computational framework, several specific genes have been identified as potential markers of smoking status in different lung cell types. These include B2M, EEF1A1, and TPT1 in lung endothelial cells; FTL and MT-ATP8 in lung epithelial cells; HLA-B and HLA-C in lung immune cells; and HSP90B1 and LCN2 in lung stroma cells. Additionally, this study developed quantitative rules for representing the gene expression patterns related to smoking. This research highlights the potential of machine learning in oncology, enhancing our molecular understanding of smoking’s harm and laying the groundwork for future mechanism-based studies.

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HLA-C and KIR permutations influence chronic obstructive pulmonary disease risk

Cited by 6 publications

References 46 publications

Effectiveness of Immunotherapy in Non-Small Cell Lung Cancer Patients with a Diagnosis of COPD: Is This a Hidden Prognosticator for Survival and a Risk Factor for Immune-Related Adverse Events?

Effectiveness of Immunotherapy in Non-Small Cell Lung Cancer Patients with a Diagnosis of COPD: Is This a Hidden Prognosticator for Survival and a Risk Factor for Immune-Related Adverse Events?

Chronic Obstructive Pulmonary Disease (COPD): Making Sense of Existing GWAS Findings in Indian Context

Machine Learning Reveals Impacts of Smoking on Gene Profiles of Different Cell Types in Lung

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