Association between germ-line HLA and immune-related adverse events

Jiang, Ning; Yu, Yue; Zhang, Min; Tang, Yu; Wu, Dawei; Wang, Shuhang; Fang, Yuan; Meng, Lin; Li, Yingying; Miao, Huilei; Ma, Peiwen; Huang, Huiyao; Li, Ning

doi:10.3389/fimmu.2022.952099

Cited by 12 publications

(15 citation statements)

References 51 publications

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“…Therefore, HLA types might be useful biomarkers in irAE risk assessments, but it is difficult to identify the association between HLA variants and the occurrence of irAEs. Heterogeneity-inducing mechanisms, such as epitope spread, loss of self-tolerance, and increased inflammatory cytokines, influence the different subtypes of irAEs ( 30 ). Further research is required to identify the role of HLA in risk assessment and the occurrence of irAEs.…”

Section: Mechanisms Of Cutaneous Iraesmentioning

confidence: 99%

Cutaneous manifestations associated with immune checkpoint inhibitors

Watanabe

Yamaguchi

2023

Front. Immunol.

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Immune checkpoint inhibitors (ICIs) are monoclonal antibodies that block key mediators of tumor-mediated immune evasion. The frequency of its use has increased rapidly and has extended to numerous cancers. ICIs target immune checkpoint molecules, such as programmed cell death protein 1 (PD-1), PD ligand 1 (PD-L1), and T cell activation, including cytotoxic T-lymphocyte-associated protein-4 (CTLA-4). However, ICI-driven alterations in the immune system can induce various immune-related adverse events (irAEs) that affect multiple organs. Among these, cutaneous irAEs are the most common and often the first to develop. Skin manifestations are characterized by a wide range of phenotypes, including maculopapular rash, psoriasiform eruption, lichen planus-like eruption, pruritus, vitiligo-like depigmentation, bullous diseases, alopecia, and Stevens-Johnson syndrome/toxic epidermal necrolysis. In terms of pathogenesis, the mechanism of cutaneous irAEs remains unclear. Still, several hypotheses have been proposed, including activation of T cells against common antigens in normal tissues and tumor cells, increased release of proinflammatory cytokines associated with immune-related effects in specific tissues/organs, association with specific human leukocyte antigen variants and organ-specific irAEs, and acceleration of concurrent medication-induced drug eruptions. Based on recent literature, this review provides an overview of each ICI-induced skin manifestation and epidemiology and focuses on the mechanisms underlying cutaneous irAEs.

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Section: Mechanisms Of Cutaneous Iraesmentioning

confidence: 99%

Cutaneous manifestations associated with immune checkpoint inhibitors

Watanabe

Yamaguchi

2023

Front. Immunol.

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“…Associations have been identified between HLA DRB1*04: 05 and ICI-induced inflammatory arthritis, HLA-DRB1*11:01 and pruritus, HLA-DQB1*03:01 and colitis (108,109). However, a recent study reported no association between HLA type and irAE development (110). Thus, further work is required toward this direction.…”

Section: Host-specific Factorsmentioning

confidence: 99%

Immune-related adverse effects of checkpoint immunotherapy and implications for the treatment of patients with cancer and autoimmune diseases

Ibis,

Aliazis,

Cao

et al. 2023

Front. Immunol.

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During the past decade, there has been a revolution in cancer therapeutics by the emergence of antibody-based immunotherapies that modulate immune responses against tumors. These therapies have offered treatment options to patients who are no longer responding to classic anti-cancer therapies. By blocking inhibitory signals mediated by surface receptors that are naturally upregulated during activation of antigen-presenting cells (APC) and T cells, predominantly PD-1 and its ligand PD-L1, as well as CTLA-4, such blocking agents have revolutionized cancer treatment. However, breaking these inhibitory signals cannot be selectively targeted to the tumor microenvironment (TME). Since the physiologic role of these inhibitory receptors, known as immune checkpoints (IC) is to maintain peripheral tolerance by preventing the activation of autoreactive immune cells, IC inhibitors (ICI) induce multiple types of immune-related adverse effects (irAEs). These irAEs, together with the natural properties of ICs as gatekeepers of self-tolerance, have precluded the use of ICI in patients with pre-existing autoimmune diseases (ADs). However, currently accumulating data indicates that ICI might be safely administered to such patients. In this review, we discuss mechanisms of well established and newly recognized irAEs and evolving knowledge from the application of ICI therapies in patients with cancer and pre-existing ADs.

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“…We further found significant differences in common immune checkpoints between the two subgroups as well ( Figure 9J ). HLA genes are also closely related to tumor immunity ( 16 ). Additionally, we examined whether HLA-related genes were expressed differently in risk subgroups.…”

Section: Resultsmentioning

confidence: 99%

Role of cuproptosis-related gene in lung adenocarcinoma

et al. 2022

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BackgroundsLung adenocarcinoma (LUAD) is the most common subtype of lung cancer, which is the leading cause of cancer death. Dysregulation of cell proliferation and death plays a crucial role in the development of LUAD. As of recently, the role of a new form of cell death, cuproptosis, and it has attracted more and more attention. As of yet, it is not clear whether cuproptosis is involved in the progression of LUAD.MethodsAn integrated set of bioinformatics tools was utilized to analyze the expression and prognostic significance of cuproptosis-related genes. Meanwhile, a robust risk signature was developed using machine learning based on prognostic cuproptosis-related genes and explored the value of prognostic cuproptosis-related signature for clinical applications, functional enrichment and immune landscape. Lastly, the dysregulation of the cuproptosis-related genes in LUAD was validated by in vitro experiment.ResultsIn this study, first, cuproptosis-related genes were found to be differentially expressed in LUAD patients of public databases, and nine of them had prognostic value. Next, a cuproptosis-related model with five features (DLTA, MTF1, GLS, PDHB and PDHA1) was constructed to separate the patients into high- and low-risk groups based on median risk score. Internal validation set and external validation set were used for model validation and evaluation. What’s more, Enrichment analysis of differential genes and the WGCNA identified that cuproptosis-related signatures affected tumor prognosis by influencing tumor immunity. Small molecule compounds were predicted based on differential expressed genes to improve poor prognosis in the high-risk group and a nomogram was constructed to further advance clinical applications. In closing, our data showed that FDX1 affected the prognosis of lung cancer by altering the expression of cuproptosis-related signature.ConclusionA new cuproptosis-related signature for survival prediction was constructed and validated by machine learning algorithm and in vitro experiments to reflect tumor immune infiltration in LUAD patients. The purpose of this article was to provide a potential diagnostic and therapeutic strategy for LUAD.

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Association between germ-line HLA and immune-related adverse events

Cited by 12 publications

References 51 publications

Cutaneous manifestations associated with immune checkpoint inhibitors

Cutaneous manifestations associated with immune checkpoint inhibitors

Immune-related adverse effects of checkpoint immunotherapy and implications for the treatment of patients with cancer and autoimmune diseases

Role of cuproptosis-related gene in lung adenocarcinoma

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