Pan-cancer analysis of the cuproptosis-related gene DBT that serves as an immunotherapy and prognostic biomarker DOI Creative Commons
Yue Cui, Hongzhi Wang,

Feng-Ying Sai

et al.

Research Square (Research Square), Journal Year: 2023, Volume and Issue: unknown

Published: June 6, 2023

Abstract Background Recently, it has been reported that Dihydrolipoamide Branched Chain Transacylase E2 (DBT) is one of the genes related to protein acylation in process cuproptosis. However, role DBT pan-cancer and its regulatory mechanism remains unclear. Methods In current study, we used a variety public bioinformatics platforms first verify expression tumor normal tissues, then further analyze relationship between prognosis cancer patients, explore action at molecular level. After that, effect on immune microenvironment pan-carcinoma was discussed. Finally, functional enrichment analysis performed. Results We found significantly down-regulated most types, upregulated predicted poor overall survival (OS) for patients pancreatic adenocarcinoma (PAAD), good OS disease free (DFS) kidney renal clear cell carcinoma (KIRC), DFS bladder urothelial carcinoma(BLCA). Further level research showed genetic alteration BLCA, ESCA acute myeloid leukemia promoter methylation also significant changes multiple tumors. positively with infiltration diverse were metabolism enzyme stability. Conclusion could be an immunotherapy prognostic biomarker cancers.

Language: Английский

Comprehensive analysis of the potential cuproptosis-related biomarker LIAS that regulates prognosis and immunotherapy of pan-cancers DOI Creative Commons
Yuan Cai, Qingchun He, Wei Liu

et al.

Frontiers in Oncology, Journal Year: 2022, Volume and Issue: 12

Published: Aug. 2, 2022

Lipoic acid synthetase (LIAS) has been demonstrated to play a crucial role in the progression of cancer. Exploring underlying mechanisms and biological functions LIAS could have potential therapeutic guidance for cancer treatment. Our study explored expression levels prognostic values pan-cancer through several bioinformatics platforms, including TIMER2.0, Gene Expression Profiling Interactive Analysis, version 2 (GEPIA2.0), Human Protein Atlas (HPA). We found that high was related good prognosis patients with kidney renal clear cell carcinoma (KIRC), rectum adenocarcinoma (READ), breast cancer, ovarian Inversely, showed unfavorable lung patients. In addition, genetic alteration, methylation levels, immune analysis evaluated. To elucidate molecular mechanism LIAS, we conduct single-cell sequencing implicate hypoxia, angiogenesis, DNA repair. Thus, these comprehensive analyses conveyed be potentially significant various cancers. Moreover, predict efficacy immunotherapy

Language: Английский

Citations

55
The role of the BTLA-HVEM complex in the pathogenesis of autoimmune diseases DOI Creative Commons
Karolina Wojciechowicz, Marta Spodzieja, Katarzyna A. Lisowska

et al.

Cellular Immunology, Journal Year: 2022, Volume and Issue: 376, P. 104532 - 104532

Published: May 5, 2022

Autoimmune diseases constitute a heterogeneous group of disorders with one common feature - the loss immune tolerance towards autoantigens. Due to complexity pathogenesis these diseases, there are still many open questions regarding their etiology. Therefore, scientists unceasingly search for new data hoping detect dependable biomarkers and design safe effective treatment. The research on checkpoints is in line scientific clinical demands. Immune may be key understanding immunological disorders. BTLA-HVEM complex, inhibitory checkpoint, has recently caught attention as an important regulator different contexts, including autoreactivity. So far, complex been mainly studied context cancer, but numerous show, it also target treating autoimmune diseases. In this review, we intend focus mechanisms interactions cells summarize available autoimmunity.

Language: Английский

Citations

33
Rheumatic Immune-Related Adverse Events due to Immune Checkpoint Inhibitors—A 2023 Update DOI Open Access
Quang Minh Dang, Ryu Watanabe,

Mayu Shiomi

et al.

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(6), P. 5643 - 5643

Published: March 15, 2023

With the aging of population, malignancies are becoming common complications in patients with rheumatoid arthritis (RA), particularly elderly patients. Such often interfere RA treatment. Among several therapeutic agents, immune checkpoint inhibitors (ICIs) which antagonize immunological brakes on T lymphocytes have emerged as a promising treatment option for variety malignancies. In parallel, evidence has accumulated that ICIs associated numerous immune-related adverse events (irAEs), such hypophysitis, myocarditis, pneumonitis, and colitis. Moreover, not only exacerbate pre-existing autoimmune diseases, but also cause de novo rheumatic disease–like symptoms, arthritis, myositis, vasculitis, currently termed irAEs. Rheumatic irAEs differ from classical diseases multiple aspects, should be individualized based severity. Close collaboration oncologists is critical preventing irreversible organ damage. This review summarizes current regarding mechanisms management focus vasculitis. Based these findings, potential strategies against discussed.

Language: Английский

Citations

21
Uncovering the flip side of immune checkpoint inhibitors: a comprehensive review of immune-related adverse events and predictive biomarkers DOI Creative Commons
Yandong Miao, Wuxia Quan, Xiaolong Tang

et al.

International Journal of Biological Sciences, Journal Year: 2024, Volume and Issue: 20(2), P. 621 - 642

Published: Jan. 1, 2024

Immune checkpoint inhibitors (ICIs) have generated considerable excitement as a novel class of immunotherapeutic agents due to their remarkable efficacy in treating various types cancer.However, the widespread use ICIs has brought about number safety concerns, especially development immune-related adverse events (irAEs).These serious complications could result treatment discontinuation and even life-threatening consequences, making it critical identify high-risk groups predictive markers irAEs before initiating therapy.To this end, current article examines several potential important organs affected by ICIs.While retrospective studies yielded some promising results, limitations such small sample sizes, variable patient populations, specific cancer studied make difficult generalize findings.Therefore, prospective cohort real-world investigations are needed validate different biomarkers predicting risk.Overall, identifying is crucial step towards improving enhancing management irAEs.With ongoing research efforts, hoped that more accurate reliable will be identified incorporated into clinical practice guide decisions prevent susceptible patients.

Language: Английский

Citations

7
Immunomodulatory Properties of Immune Checkpoint Inhibitors—More than Boosting T-Cell Responses? DOI Open Access
Michael Kuske, Maximilian Haist,

T. Jung

et al.

Cancers, Journal Year: 2022, Volume and Issue: 14(7), P. 1710 - 1710

Published: March 28, 2022

The approval of immune checkpoint inhibitors (ICI) that serve to enhance effector T-cell anti-tumor responses has strongly improved success rates in the treatment metastatic melanoma and other tumor types. currently approved ICI constitute monoclonal antibodies blocking cytotoxic T-lymphocyte-associated protein (CTLA)-4 anti-programmed cell death (PD)-1. By this, T-cell-inhibitory CTLA-4/CD80/86 PD-1/PD-1L/2L signaling axes are inhibited. This leads sustained activity circumvents evasion cells, which frequently upregulate PD-L1 expression modulate molecule on leukocytes. As a result, profound clinical observed 40–60% patients. Despite pivotal role T cells for triggering immunity, mounting evidence indicates efficacy may also be attributable types than cells. In particular, emerging research shown impacts innate such as myeloid natural killer lymphoid amplify tumoricidal functions beyond thus improves efficacy. Effects non-T additionally explain, part, character extent adverse effects associated with treatment. Deeper knowledge these is required further develop terms responsiveness patients treatment, overcome resistance alleviate effects. this review we give an overview into known immunomodulatory compartment.

Language: Английский

Citations

24
Targeting immune checkpoints in anti-neutrophil cytoplasmic antibodies associated vasculitis: the potential therapeutic targets in the future DOI Creative Commons
Menglu Pan, Huanhuan Zhao,

Ruimin Jin

et al.

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: April 6, 2023

Anti-neutrophil cytoplasmic autoantibodies (ANCA) associated vasculitis (AAV) is a necrotizing mainly involving small blood vessels. It demonstrated that T cells are important in the pathogenesis of AAV, including regulatory (Treg) and helper (Th), especially Th2, Th17, follicular Th (Tfh). In addition, exhaustion predicted favorable prognosis AAV. The immune checkpoints (ICs) consist group co-stimulatory co-inhibitory molecules expressed on surface cells, which maintains balance between activation cells. CD28, inducible T-cell co-stimulator (ICOS), OX40, CD40L, glucocorticoid induced tumor necrosis factor receptor (GITR), CD137 common molecules, while programmed cell death 1 (PD-1), cytotoxic lymphocyte-associated molecule 4 (CTLA-4), immunoglobulin (Ig) mucin domain-containing protein 3 (TIM-3), B lymphocyte attenuator (BTLA), V-domain Ig suppressor (VISTA), T‐cell ITIM domain (TIGIT), CD200, gene (LAG-3) belong to molecules. If this was disrupted increased, autoimmune diseases (AIDs) might be induced. Even treatment malignant tumors, by checkpoint inhibitors (ICIs) may result AIDs known as rheumatic immune-related adverse events (Rh-irAEs), suggesting importance ICs AIDs. review, we summarized features AAV immunotherapy using ICIs patients with then reviewed biological characteristics different ICs. Our aim explore potential targets for future

Language: Английский

Citations

11
Immunotherapy Complications DOI
Alexa Meara,

Jaclyn Zois,

Jason J. Bischof

et al.

Emergency Medicine Clinics of North America, Journal Year: 2025, Volume and Issue: unknown

Published: April 1, 2025

Language: Английский

Citations

0
Clinical Patterns and Follow-Up of Inflammatory Arthritis and Other Immune-Related Adverse Events Induced by Checkpoint Inhibitors. A Multicenter Study DOI Creative Commons
José A. Gómez‐Puerta, David Lobo, Carolina Pérez-García

et al.

Frontiers in Medicine, Journal Year: 2022, Volume and Issue: 9

Published: June 15, 2022

To describe different clinical patterns of rheumatic immune-related adverse events (irAEs) induced by immune checkpoint inhibitors (ICI) and their oncologic outcomes.We classified syndromes according to five categories: non-inflammatory arthralgias (NIA), rheumatoid arthritis (RA)-like, psoriatic (PsA)-like, polymyalgia rheumatica (PMR)-like, a miscellaneous group patients with other syndromes. We conducted baseline visit then follow-up in order determine pattern, treatment response, outcome.We included 73 (64% male) mean age 66.1 ± 11.6 years. Main underlying diagnosis was lung carcinoma 29 (39%) patients, melanoma 20 (27%), renal-urothelial cancer 11 (15%). ICI Pembrolizumab 24 (32%), Nivolumab 17 (23%), Atezolizumab 7 (9 %). Seventeen out seventy-three had an disease before treatment. Fourteen developed irAEs or simultaneously included: RA-like 31 (42.4%), NIA 19 (26.0%), PMR-like 10 (13.7%), PsA-like 5 (6.8%), among others. Median time from months (IQR 3-9). Those who received combined therapy, trend for earlier presentation than those monotherapy (4.3 IQR 1.85-17 vs. 6 3-9.25, p = NS). Mean 14.0 10.8 (SD, months). At the last visit, 47 % were taking glucocorticoids 11% DMARD therapy. 13 (17.8%) remained persistent arthritis, (26%) intermittent flares, 39 (53.4%) self-limited pattern. Only 15.1% therapy discontinued.We described irAEs. Combined onset symptoms. Patients presented as RA-like, higher risk arthritis. After more 1 year, one-fifth required

Language: Английский

Citations

16
Neurologic manifestations of autoimmunity with immune checkpoint inhibitors DOI
Jennifer A. McCombe, Elia Sechi, Αναστασία Ζεκερίδου

et al.

Handbook of clinical neurology, Journal Year: 2024, Volume and Issue: unknown, P. 449 - 465

Published: Jan. 1, 2024

Language: Английский

Citations

3
Programmed Death Ligand 1–Expressing Macrophages and Their Protective Role in the Joint During Arthritis DOI
Megan Kay Wood, Abdel Daoud, Monica V. Talor

et al.

Arthritis & Rheumatology, Journal Year: 2023, Volume and Issue: 76(4), P. 553 - 565

Published: Nov. 24, 2023

Objective Arthritis associated with immune checkpoint inhibitor therapies highlights the importance of expression for joint homeostasis. We investigated role programmed death ligand (PD‐L) 1 in synovium using a collagen‐induced arthritis (CIA) mouse model. Methods blocked PD‐L1 blocking antibodies during CIA and assessed severity by clinical histologic scoring. origin synovial macrophages were flow cytometry parabiosis. used Cre‐Lox mice to ascertain protective PD‐L1–expressing arthritis. The profile human murine + was determined reverse transcriptase–polymerase chain reaction, cytometry, single‐cell RNA sequencing. Results Anti–PD‐L1 antibody treatment worsened increased cell infiltration compared isotype control, supporting regulatory joint. main cells expressing macrophages. Using parabiosis, we showed that both locally proliferating partially replaced circulation. had levels MER proto‐oncogene tyrosine kinase (MerTK) interleukin (IL)‐10 acute CIA. Genetic depletion on Lyz cre fl/fl resulted controls. found healthy individuals patients rheumatoid express MerTK IL‐10. Conclusion efferocytotic anti‐inflammatory characteristics protect from severe Tissue‐protective, are also present at homeostasis

Language: Английский

Citations

8