Novel post-translational modification learning signature reveals B4GALT2 as an immune exclusion regulator in lung adenocarcinoma

Journal for ImmunoTherapy of Cancer, Journal Year: 2025, Volume and Issue: 13(2), P. e010787 - e010787

Published: Feb. 1, 2025

Background Lung adenocarcinoma (LUAD) presents significant challenges in prognosis and treatment efficacy evaluation. While post-translational modifications are known to influence tumor progression, their prognostic value LUAD remains largely unexplored. Methods We developed a modification learning signature (PTMLS) using machine techniques, analyzing data from 1231 patients across seven global cohorts. The signature’s predicting immunotherapy response was evaluated 12 cohorts spanning multiple cancer types (n=1201). An in-house tissue cohort (n=171) used validate beta-1,4-galactosyltransferase 2’s (B4GALT2’s) significance. role of B4GALT2 immune exclusion investigated through vivo vitro experiments. Results established PTMLS exhibited exceptional predictive capabilities patient outcomes, surpassing the 98 existing indicators. system’s validated diverse malignancy categories for immunotherapeutic assessment. From biological perspective, correlations were observed between immunological parameters, whereby elevated levels characterized by attenuated responses immunologically cold neoplastic features. Within framework, identified as crucial molecular component (r=0.82, p<0.05), its heightened expression linked unfavorable clinical outcomes cases, particularly specimens exhibiting CD8-depleted phenotypes. spatial distribution patterns cell populations, specifically CD8+ T lymphocytes CD20+ B lymphocytes, elucidated multiplexed immunofluorescence analysis. Laboratory investigations subsequently B4GALT2’s regulatory on cellular expansion both laboratory cultures animal models. Significantly, suppression found enhance lymphocyte populations functional status, thereby potentiating anti-programmed death protein 1 studies. This phenomenon reduced CD62L+CD8 alongside GZMB+/CD44+/CD69+CD8 populations. Conclusion system represents an effective instrument individualized evaluation stratification identification previously unrecognized oncogenic factor involved novel therapeutic avenue optimization.

Language: Английский

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The therapeutic potential of PD-1/PD-L1 pathway on immune-related diseases: Based on the innate and adaptive immune components

Biomedicine & Pharmacotherapy, Journal Year: 2023, Volume and Issue: 167, P. 115569 - 115569

Published: Sept. 26, 2023

Currently, immunotherapy targeting programmed cell death 1 (PD-1) or ligand (PD-L1) has revolutionized the treatment strategy of human cancer patients. Meanwhile, PD-1/PD-L1 pathway also been implicated in pathogenesis many immune-related diseases, such as autoimmune chronic infection diseases and adverse pregnancy outcomes, by regulating components innate adaptive immune systems. Given power new therapy, a better understanding regulatory effects on responses will facilitate discovery novel biomarkers therapeutic drug targets. Targeting this may successfully halt potentially even reverse these pathological processes. In review, we discuss recent major advances axis diseases. We reveal that impact system is complex manifold multi-strategies targeted are taken Consequently, pathway, alone combination with other treatments, represent for future intervention

Language: Английский

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Efficacy and Safety Assessment of Intrathoracic Perfusion Chemotherapy Combined with immunological factor Interleukin-2 in the Treatment of Advanced Non-Small Cell Lung Cancer: A Retrospective Cohort Study

Journal of Cancer, Journal Year: 2024, Volume and Issue: 15(7), P. 2024 - 2032

Published: Jan. 1, 2024

Objective: This study evaluated the efficacy and safety of gemcitabine oxaliplatin intrathoracic perfusion chemotherapy (IPCGOR) regimen combined with interleukin-2 (IL-2) for advanced non-small cell lung cancer (NSCLC).Methods: We conducted a retrospective analysis 460 NSCLC patients from Yunnan Province Early Cancer Diagnosis Treatment Project (June 2020-October 2022), assessing IPCGOR IL-2 combination.Outcomes were measured based on RECIST 1.1 criteria, focusing objective response rate (ORR), disease control (DCR), median progression-free survival (mPFS), overall (MOS), treatment safety.Results: The demonstrated an ORR 67.4%, DCR 97.4%, mPFS 8.5 months, MOS 12.5 months.14 underwent successful surgery post-treatment.Common adverse reactions manageable, no treatment-related deaths reported. Conclusion:The shows promising tolerable profile NSCLC.These findings suggest its potential as reference treating NSCLC.However, study's nature single-center design pose limitations.Future research should focus prospective studies, randomized controlled trials, long-term outcome assessments, particularly in diverse patient subgroups, to further validate refine clinical application this regimen.

Language: Английский

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Recent Advances in Biomimetic Strategies for the Immunotherapy of Glioblastoma

Biomaterials, Journal Year: 2024, Volume and Issue: 311, P. 122694 - 122694

Published: June 28, 2024

Language: Английский

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Innovative Formulation Platform: Paving the Way for Superior Protein Therapeutics with Enhanced Efficacy and Broadened Applications

Advanced Materials, Journal Year: 2024, Volume and Issue: 36(41)

Published: May 31, 2024

Abstract Protein therapeutics offer high therapeutic potency and specificity; the broader adoptions development of protein therapeutics, however, have been constricted by their intrinsic limitations such as inadequate stability, immunogenicity, suboptimal pharmacokinetics biodistribution, off‐target effects. This review describes a platform technology that formulates individual molecules with thin formulation layer crosslinked polymers, which confers activity, enhanced controlled release capability, reduced improved ability to cross blood brain barriers. Based on currently approved this formulating affords vast family superior efficacy broadened indications at significantly cost.

Language: Английский

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PTMs of PD-1/PD-L1 and PROTACs application for improving cancer immunotherapy

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: April 4, 2024

Immunotherapy has been developed, which harnesses and enhances the innate powers of immune system to fight disease, particularly cancer. PD-1 (programmed death-1) PD-L1 death ligand-1) are key components in regulation system, context cancer immunotherapy. regulated by PTMs, including phosphorylation, ubiquitination, deubiquitination, acetylation, palmitoylation glycosylation. PROTACs (Proteolysis Targeting Chimeras) a type new drug design technology. They specifically engineered molecules that target specific proteins within cell for degradation. have designed demonstrated their inhibitory activity against PD-1/PD-L1 pathway, showed ability degrade proteins. In this review, we describe how improve efficacy could be novel strategy combine with radiotherapy, chemotherapy immunotherapy patients.

Language: Английский

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Nanomedicine-based adjuvant therapy: a promising solution for lung cancer

Journal of Nanobiotechnology, Journal Year: 2023, Volume and Issue: 21(1)

Published: July 6, 2023

Abstract Lung cancer has been the leading cause of cancer-related deaths worldwide for decades. Despite increasing understanding underlying disease mechanisms, prognosis still remains poor many patients. Novel adjuvant therapies have emerged as a promising treatment method to augment conventional methods and boost therapeutic effects primary therapies. Adjuvant therapy based on nanomedicine gained considerable interest supporting enhancing traditional therapies, such chemotherapy, immunotherapy, radiotherapy, due tunable physicochemical features ease synthetic design nanomaterials. In addition, can provide protective against other by reducing adverse side through precise targeting. Therefore, nanomedicine-based extensively employed in wide range preclinical clinical treatments overcome drawbacks this review, we mainly discuss recent advances lung highlight their functions improving outcome which may inspire new ideas advanced stimulate research efforts around topic. Graphical

Language: Английский

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A real-world pharmacovigilance study of FDA adverse event reporting system events for Capmatinib

Scientific Reports, Journal Year: 2024, Volume and Issue: 14(1)

Published: May 18, 2024

Abstract Capmatinib is a potent selective mesenchymal-epithelial transition inhibitor approved in 2020 for the treatment of metastatic non-small cell lung cancer. As real-world evidence very limited, this study evaluated capmatinib-induced adverse events through data mining FDA Adverse Event Reporting System database. Four disproportionality analysis methods were employed to quantify signals capmatinib-related events. The difference capmatinib-associated event was further investigated with respect sex, age, weight, dose, onset time, continent, and concomitant drug. A total 1518 reports 4278 induced by capmatinib identified. New significant emerged, such as dysphagia, dehydration, deafness, vocal cord paralysis, muscle disorder, oesophageal stenosis. Notably, higher risk alanine aminotransferase aspartate increases observed females, especially when combined immune checkpoint inhibitors. Compared Europeans Asians, Americans more likely experience peripheral swelling, people > 65 years age. Renal impairment increased blood creatinine occur single doses above 400 mg Asians. This improves understanding safety profile capmatinib.

Language: Английский

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Harnessing Natural Killer Cells for Lung Cancer Therapy

Cancer Research, Journal Year: 2023, Volume and Issue: 83(20), P. 3327 - 3339

Published: Aug. 2, 2023

Abstract Lung cancer is the leading cause of cancer-related death worldwide. Although natural killer (NK) cells are garnering interest as a potential anticancer therapy because they selectively recognize and eliminate cells, their use in treating solid tumors, including lung cancer, has been limited due to impediments efficacy, such ability reach tumor tissues, reduced antitumor activity tumor-infiltrating NK suppressive microenvironment (TME). This comprehensive review provides an in-depth analysis cross-talk between TME cells. We highlight various mechanisms used by modulate NK-cell phenotypes limit infiltration, explore role limiting discuss current challenges obstacles that hinder success NK-cell–based immunotherapy for cancer. Potential opportunities promising strategies address these have implemented or being developed optimize Through critical evaluation existing literature emerging trends, this outlook on future

Language: Английский

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Targeting immune cell types of tumor microenvironment to overcome resistance to PD-1/PD-L1 blockade in lung cancer

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

Published: Feb. 15, 2023

Lung cancer is the common malignant tumor with highest mortality rate. patients have achieved benefits from immunotherapy, including immune checkpoint inhibitors (ICIs) therapy. Unfortunately, acquire adaptive resistance, leading to poor prognosis. Tumor microenvironment (TME) has been demonstrated play a critical role in participating acquired resistance. TME associated molecular heterogeneity of immunotherapy efficacy lung cancer. In this article, we discuss how cell types are correlated Moreover, describe driven gene mutations cancer, KRAS, TP53, EGFR, ALK, ROS1, KEAP1, ZFHX3, PTCH1, PAK7, UBE3A, TNF-α, NOTCH, LRP1B, FBXW7, and STK11. We also emphasize that modulation could be promising strategy for improving resistance

Language: Английский

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