The landscape of <i>CD28, CD80, CD86, CTLA4</i>, and <i>ICOS</i> DNA methylation in head and neck squamous cell carcinomas

Vos, Luka de; Grünwald, Ingela; Bawden, Emma Grace; Dietrich, Jörn; Scheckenbach, Kathrin; Wiek, Constanze; Zarbl, Romina; Bootz, Friedrich; Landsberg, Jennifer; Dietrich, Dimo

doi:10.1080/15592294.2020.1754675

Cited by 35 publications

(30 citation statements)

References 67 publications

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“…First, aberrant methylation causes abnormal mRNA expression. The CD28, CTLA4, CD80, and CD86 expression values are mediated by DNA methylation [ 85 ]. The positive or negative correlation between the expression levels of those checkpoints and methylation levels depends on the specific CpG sites [ 85 ].…”

Section: Discussionmentioning

confidence: 99%

“…The CD28, CTLA4, CD80, and CD86 expression values are mediated by DNA methylation [ 85 ]. The positive or negative correlation between the expression levels of those checkpoints and methylation levels depends on the specific CpG sites [ 85 ]. However, a previous publication showed a significantly positive correlation between the PD-L1 promoter methylation level and protein expression level in advanced gastric cancer [ 86 ].…”

Section: Discussionmentioning

confidence: 99%

“…The high TMB, non-small-cell lung cancer group had more DNA methylation aberrations, including hypermethylation [ 89 ]. The correlation between TMB and the DNA methylation level was negative in head and neck squamous cell carcinomas [ 85 ]. Unlike the previous study, in the present study, TMB demonstrated a remarkable difference only between cluster 1 and cluster 2.…”

Section: Discussionmentioning

confidence: 99%

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A Methylation-Based Reclassification of Bladder Cancer Based on Immune Cell Genes

Luo

Vögeli

2020

Cancers

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Background: Bladder cancer is highly related to immune cell infiltration. This study aimed to develop a new classification of BC molecular subtypes based on immune-cell-associated CpG sites. Methods: The genes of 28 types of immune cells were obtained from previous studies. Then, methylation sites corresponding to immune-cell-associated genes were acquired. Differentially methylated sites (DMSs) were identified between normal samples and bladder cancer samples. Unsupervised clustering analysis of differentially methylated sites was performed to divide the sites into several subtypes. Then, the potential mechanism of different subtypes was explored. Results: Bladder cancer patients were divided into three groups. The cluster 3 subtype had the best prognosis. Cluster 1 had the poorest prognosis. The distribution of immune cells, level of expression of checkpoints, stromal score, immune score, ESTIMATEScore, tumor purity, APC co_inhibition, APC co_stimulation, HLA, MHC class_I, Type I IFN Response, Type II IFN Response, and DNAss presented significant differences among the three subgroups. The distribution of genomic alterations was also different. Conclusions: The proposed classification was accurate and stable. BC patients could be divided into three subtypes based on the immune-cell-associated CpG sites. Specific biological signaling pathways, immune mechanisms, and genomic alterations were varied among the three subgroups. High-level immune infiltration was correlated with high-level methylation. The lower RNAss was associated with higher immune infiltration. The study of the intratumoral immune microenvironment may provide a new perspective for BC therapy.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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A Methylation-Based Reclassification of Bladder Cancer Based on Immune Cell Genes

Luo

Vögeli

2020

Cancers

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“…Next to the PD1/PD-L1 pathways, some drugs targeting these distinct mechanisms are currently in preclinical studies, in clinical phase I and II trials as single agent or in combination with other checkpoint molecules or already approved for the treatment of HNSCCs. These include antibodies directed against LAG-3, TIM-3, TIGIT and ICOS [ 90 , 118 , 119 , 120 ]. In addition, a bifunctional fusion protein to block PD-L1 and TGF-β receptor has been applied in a phase I trial demonstrating a clinical activity [ 121 ].…”

Section: Therapeutic Strategies To Overcome Immune Escape Mechanismentioning

confidence: 99%

Immune Escape Mechanisms and Their Clinical Relevance in Head and Neck Squamous Cell Carcinoma

Seliger

Massa

Yang

et al. 2020

IJMS

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Immunotherapy has been recently approved for the treatment of relapsed and metastatic human papilloma virus (HPV) positive and negative head and neck squamous cell carcinoma (HNSCC). However, the response of patients is limited and the overall survival remains short with a low rate of long-term survivors. There exists growing evidence that complex and partially redundant immune escape mechanisms play an important role for the low efficacy of immunotherapies in this disease. These are caused by diverse complex processes characterized by (i) changes in the expression of immune modulatory molecules in tumor cells, (ii) alterations in the frequency, composition and clonal expansion of immune cell subpopulations in the tumor microenvironment and peripheral blood leading to reduced innate and adaptive immune responses, (iii) impaired homing of immune cells to the tumor site as well as (iv) the presence of immune suppressive soluble and physical factors in the tumor microenvironment. We here summarize the major immune escape strategies of HNSCC lesions, highlight pathways, and molecular targets that help to attenuate HNSCC-induced immune tolerance, affect the selection and success of immunotherapeutic approaches to overcome resistance to immunotherapy by targeting immune escape mechanisms and thus improve the HNSCC patients’ outcome.

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“…Next to the PD1/PD-L1 pathways, some drugs targeting these distinct mechanisms are currently in preclinical studies, in clinical phase I and II trials as single agent or in combination with other checkpoint molecules or already approved for the treatment of HNSCCs. These include antibodies directed against LAG-3, TIM-3, TIGIT and ICOS [68] [93] [94] [95]. In addition, a bifunctional fusion protein to block PD-L1 and TGF-β receptor has been applied in a phase I trial demonstrating a clinical activity [96].…”

Section: Therapeutic Strategies To Overcome Immune Escape Mechanisms mentioning

confidence: 99%

Immune Escape Mechanisms and Their Clinical Relevance in Head and Neck Squamous Cell Carcinoma

Seliger

Massa

Yang

et al. 2020

Preprint

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β2-m, β2-microglobulin; CAF, cancer associated fibroblast; CSC, cancer stem cell; CTL, cytotoxic T lymphocyte; DC, dendritic cell; ECM, extracellular matrix; EGF-R, epidermal growth factor receptor; ER, endoplasmic reticulum; FDA, Food and Drug Administration; HLA, human leukocyte antigen; HNSCC, head and neck squamous cell carcinoma; HPV, human papilloma virus; ICP immune checkpoint; ICPi, immune checkpoint inhibitor; IFN, interferon; LMP, low molecular weight protein; mAb, monoclonal antibody; MDSC, myeloid-derived suppressor cell; mTOR, mammalian target of rapamycin; MSI, multispectral imaging; NK, natural killer; OS, overall survival; PBL, peripheral blood lymphocytes; PBMNC, peripheral blood mononuclear cells; PD1, programmed death receptor 1; PD-L1, programmed death ligand 1; PFS, progression-free survival; PI3K, phosphatidyl-linositol-3-kinase; R/M, recurrence and or metastatic; STAT, signal transducer and activator of transcription; TAA, tumor-associated antigen; TAM, tumor associated macrophages; TAP, transporter associated with antigen processing; TCR, T cell receptor; TIL, tumor-infiltrating lymphocyte; TLS, tertiary lymphoid structure; TME, tumor microenvironment; Treg, regulatory T cell; TSA, tumor-specific antigen; VEGF, vascular endothelial growth factor; VEGF-R, vascular endothelial growth factor receptor.

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The landscape of CD28, CD80, CD86, CTLA4, and ICOS DNA methylation in head and neck squamous cell carcinomas

Cited by 35 publications

References 67 publications

A Methylation-Based Reclassification of Bladder Cancer Based on Immune Cell Genes

A Methylation-Based Reclassification of Bladder Cancer Based on Immune Cell Genes

Immune Escape Mechanisms and Their Clinical Relevance in Head and Neck Squamous Cell Carcinoma

Immune Escape Mechanisms and Their Clinical Relevance in Head and Neck Squamous Cell Carcinoma

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