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Major histocompatibility complex class II molecule in non-small cell lung cancer diagnosis, prognosis and treatment.

ABSTRACT: Lung cancer is one of the commonest cancers in the world. More than 70% of lung cancer patients are diagnosed with non-small cell lung cancer (NSCLC). Major histocompatibility complex class II (MHC class II), an important component in antigen presenting process, usually expresses on professional antigen presenting cells (APCs), and it can be induced by interferon-? (IFN-?). MHC class II can be expressed by NSCLC cells. In NSCLC patients, the expression of MHC class II can be correlated with the outcome of anti-programmed death-1 (anti-PD-1) therapy. This review summarizes MHC class II expression in NSCLC and the correlation between MHC class II and NSCLC diagnosis, prognosis and therapy.

SUBMITTER: Wang H

PROVIDER: S-EPMC6733341 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Major histocompatibility complex class II molecule in non-small cell lung cancer diagnosis, prognosis and treatment.

Wang Hao H Zhao Sha S Zhang Xiaoshen X Jia Keyi K Deng Juan J Zhou Caicun C He Yayi Y

OncoTargets and therapy 20190905

Lung cancer is one of the commonest cancers in the world. More than 70% of lung cancer patients are diagnosed with non-small cell lung cancer (NSCLC). Major histocompatibility complex class II (MHC class II), an important component in antigen presenting process, usually expresses on professional antigen presenting cells (APCs), and it can be induced by interferon-γ (IFN-γ). MHC class II can be expressed by NSCLC cells. In NSCLC patients, the expression of MHC class II can be correlated with the ...[more]

PMID: 31564911

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Project description:Sirenians share with cetaceans and pinnipeds several convergent traits selected for the aquatic lifestyle. Living in water poses new challenges not only for locomotion and feeding but also for combating new pathogens, which may render the immune system one of the best tools aquatic mammals have for dealing with aquatic microbial threats. So far, only cetaceans have had their class II Major Histocompatibility Complex (MHC) organization characterized, despite the importance of MHC genes for adaptive immune responses. This study aims to characterize the organization of the marine mammal class II MHC using publicly available genomes. We located class II sequences in the genomes of one sirenian, four pinnipeds and eight cetaceans using NCBI-BLAST and reannotated the sequences using local BLAST search with exon and intron libraries. Scaffolds containing class II sequences were compared using dotplot analysis and introns were used for phylogenetic analysis. The manatee class II region shares overall synteny with other mammals, however most DR loci were translocated from the canonical location, past the extended class II region. Detailed analysis of the genomes of closely related taxa revealed that this presumed translocation is shared with all other living afrotherians. Other presumptive chromosome rearrangements in Afrotheria are the deletion of DQ loci in Afrosoricida and deletion of DP in E. telfairi. Pinnipeds share the main features of dog MHC: lack of a functional pair of DPA/DPB genes and inverted DRB locus between DQ and DO subregions. All cetaceans share the Cetartiodactyla inversion separating class II genes into two subregions: class IIa, with DR and DQ genes, and class IIb, with non-classic genes and a DRB pseudogene. These results point to three distinct and unheralded class II MHC structures in marine mammals: one canonical organization but lacking DP genes in pinnipeds; one bearing an inversion separating IIa and IIb subregions lacking DP genes found in cetaceans; and one with a translocation separating the most diverse class II gene from the MHC found in afrotherians and presumptive functional DR, DQ, and DP genes. Future functional research will reveal how these aquatic mammals cope with pathogen pressures with these divergent MHC organizations.

Project description:BACKGROUND:CD4+ T cells play an important role in atherosclerosis, but their antigen specificity is poorly understood. Immunization with apolipoprotein B (ApoB, core protein of low density lipoprotein) is known to be atheroprotective in animal models. Here, we report on a human APOB peptide, p18, that is sequence-identical in mouse ApoB and binds to both mouse and human major histocompatibility complex class II molecules. METHODS:We constructed p18 tetramers to detect human and mouse APOB-specific T cells and assayed their phenotype by flow cytometry including CD4 lineage transcription factors, intracellular cytokines, and T cell receptor activation. Apolipoprotein E-deficient ( Apoe-/-) mice were vaccinated with p18 peptide or adjuvants alone, and atherosclerotic burden in the aorta was determined. RESULTS:In human peripheral blood mononuclear cells from donors without cardiovascular disease, p18 specific CD4+ T cells detected by a new human leukocyte antigen-antigen D related-p18 tetramers were mostly Foxp3+ regulatory T cells (Tregs). Donors with subclinical cardiovascular disease as detected by carotid artery ultrasound had Tregs coexpressing retinoic acid-related orphan receptor gamma t or T-bet, which were both almost absent in donors without cardiovascular disease. In Apoe-/- mice, immunization with p18 induced Tregs and reduced atherosclerotic lesions. After peptide restimulation, responding CD4+ T cells identified by Nur77-GFP (green fluorescent protein) were highly enriched in Tregs. A new mouse I-Ab-p18 tetramer identified the expansion of p18-specific CD4+ T cells on vaccination, which were enriched for interleukin-10-producing Tregs. CONCLUSIONS:These findings show that APOB p18-specific CD4+ T cells are mainly Tregs in healthy donors, but coexpress other CD4 lineage transcription factors in donors with subclinical cardiovascular disease. This study identifies ApoB peptide 18 as the first Treg epitope in human and mouse atherosclerosis.

Dataset Information

Major histocompatibility complex class II molecule in non-small cell lung cancer diagnosis, prognosis and treatment.

Publications

Major histocompatibility complex class II molecule in non-small cell lung cancer diagnosis, prognosis and treatment.

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