Programmed death receptor (PD-)1/PD-ligand (L)1 in urological cancers : the “all-around warrior” in immunotherapy

Molecular Cancer, Journal Year: 2024, Volume and Issue: 23(1)

Published: Sept. 2, 2024

Programmed death receptor-1 (PD-1) and its ligand, programmed ligand-1 (PD-L1) are essential molecules that key in modulating immune responses. PD-L1 is constitutively expressed on various cells, epithelial cancer where it functions as a co-stimulatory molecule capable of impairing T-cell mediated Upon binding to PD-1 activated T-cells, the PD-1/PD-L1 interaction triggers signaling pathways can induce apoptosis or anergy, thereby facilitating escape tumors. In urological cancers, including bladder (BCa), renal cell carcinoma (RCC), prostate (PCa), upregulation has been demonstrated. It linked poor prognosis enhanced tumor evasion. Recent studies have highlighted significant role axis mechanisms cancers. The between T-cells further contributes immunosuppression by inhibiting activation proliferation. Clinical applications checkpoint inhibitors shown promising efficacy treating advanced significantly improving patient outcomes. However, resistance these therapies, either intrinsic acquired, remains challenge. This review aims provide comprehensive overview pathway We summarize regulatory mechanism underlying expression activity, genetic, epigenetic, post-transcriptional, post-translational modifications. Additionally, we discuss current clinical research inhibitors, their therapeutic potential, challenges associated with resistance. Understanding crucial for developing new strategies overcome limitations enhance immunotherapy.

Language: Английский

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The role of B2M in cancer immunotherapy resistance: function, resistance mechanism, and reversal strategies

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: March 21, 2025

Immunotherapy has emerged as a preeminent force in the domain of cancer therapeutics and achieved remarkable breakthroughs. Nevertheless, high resistance become most substantial impediment restricting its clinical efficacy. Beta-2 microglobulin (B2M), light chain major histocompatibility complex (MHC) class I, plays an indispensable part by presenting tumor antigens to cytotoxic T lymphocytes (CTLs) for exerting anti-tumor effects. Accumulating evidence indicates that B2M mutation/defect is one key mechanisms underlying immunotherapy resistance. Therefore, elucidating role played devising effective strategies battle against are pressing issues. This review will systematically expound upon them, aiming provide insight into potential promising target anticancer immune response.

Language: Английский

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Regulatory T cells in immune checkpoint blockade antitumor therapy

Molecular Cancer, Journal Year: 2024, Volume and Issue: 23(1)

Published: Nov. 8, 2024

Regulatory T cells (Tregs), an essential component of the human immune system, are a heterogeneous group lymphocytes with ability to suppress responses and maintain homeostasis. Recent evidence indicates that Tregs may impair antitumor immunity facilitate cancer progression by weakening functions effector (Teffs). Consequently, targeting eliminate them from tumor microenvironments improve Teffs' activity could emerge as effective strategy for immunotherapy. This review outlines biology Tregs, detailing their origins, classification, crucial markers. Our focus lies on complex role in cancer's development, treatment, particularly suppressive upon via multiple mechanisms. We delve into Tregs' involvement checkpoint blockade (ICB) therapy, dual effect immunotherapy potential biomarkers ICB therapy effectiveness. also summarize advances therapies adjust optimize which be devising innovative treatment strategies.

Language: Английский

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Global research trends on biomarkers for cancer immunotherapy: Visualization and bibliometric analysis

Human Vaccines & Immunotherapeutics, Journal Year: 2025, Volume and Issue: 21(1)

Published: Jan. 8, 2025

The global burden of cancer continues to grow, posing a significant public health challenge. Although immunotherapy has shown efficacy, the response rate is not high. Therefore, objective our research was identify latest trends and hotspots on biomarkers from 1993 2023. Data were collected database Web Science core collection. Bibliometric analysis visualization conducted with CiteSpace(6.3.1), VOSviewer (v1.6.20), R-bibliometrix(v4.3.3), Microsoft Excel(2019). A total 2686 literatures retrieved. sheer annual volume publications rapid upward trend since 2015. United States generated most Harvard University ranked as leading institution. biomarker immune checkpoint inhibitors (ICIs) revealed regional differences in-depth explorations should be promoted in developing countries. China become second largest country terms publication, average citation per paper link strength both lower than other mainly concentrated upon following aspects: PD-1/PD-L1, CTLA-4, gene expression, adverse events, mutational (TMB), body mass index (BMI), gut microbiota, cd8(+)/cd4(+) t-cells, blood-related such lactate dehydrogenase (LDH), neutrophil–lymphocyte ratio (NLR), cytokines. Furthermore, "artificial intelligence" "machine learning" have important hotspot over last 2 y, which will help us useful complex big data provide basis for precise medicine malignant tumors.

Language: Английский

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Ultrasound-Guided Histotripsy Triggers the Release of Tumor-Associated Antigens from Breast Cancers

Cancers, Journal Year: 2025, Volume and Issue: 17(2), P. 183 - 183

Published: Jan. 8, 2025

Background/Objectives: There is increasing evidence to indicate that histotripsy treatment can enhance the host anti-tumor immune responses both locally at targeting tumor site as well systemically from abscopal effects. Histotripsy a non-invasive ultrasound ablation technology mechanically disrupts target tissue via cavitation. A key factor contributing histotripsy-induced effects believed be release of tumor-specific antigens (TSAs) or tumor-associated (TAAs) induce systemic response. In this study, we studied effect on HER2, well-defined TAA for cancer immunotherapy. Methods: range doses administered HER2-postive mammary cells in an vitro cell culture system and ex vivo were applied. addition, single dose was used murine model. The released proteins, specifically cell-free supernatants pellets analyzed by BCA protein assay, ultra-performance liquid chromatography (UPLC) Western blot. Results: Our results showed could significantly trigger HER2 proteins current study. level actually higher than pellets, suggesting intracellular domain into extracellular compartment. Furthermore, proportionally more doses, indicating free histotripsy-dose-dependent. Conclusions: conclusion, have qualitatively quantitatively demonstrated triggers histotripsy-mediated provides important insights mechanism underlying its immunostimulation suggests potential TSA/TAA-based immunotherapies numerous types.

Language: Английский

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Silicasomes in Oncology: From Conventional Chemotherapy to Combined Immunotherapy

Molecules, Journal Year: 2025, Volume and Issue: 30(6), P. 1257 - 1257

Published: March 11, 2025

The use of nanoparticles as drug carriers in oncology has evolved from their traditional role chemotherapy to application immunotherapy, exploiting not only passive accumulation solid tumors but also ability interact with immune cells. Silicasomes are highly versatile nanoplatforms composed a mesoporous silica core whose external surface is coated lipid bilayer that allows the co-delivery therapeutic agents having different chemical natures (small molecules, proteins, enzymes, or oligonucleotides, among others). Herein, cutting-edge advances carried out development and silicasomes presented, providing general description performance these nanotransporters. Additionally, specific load chemotherapeutic drugs explored, followed by discussion immunotherapeutic combination strategies, including theragnosis, single silicasome platform, highlighting enormous potential nanosystems.

Language: Английский

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Monoclonal antibody immune therapy response instrument for stratification and cost-effective personalized approaches in 3PM-guided pan cancer management

The EPMA Journal, Journal Year: 2025, Volume and Issue: unknown

Published: March 22, 2025

Language: Английский

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The Benefits and Safety of Monoclonal Antibodies: Implications for Cancer Immunotherapy

Journal of Inflammation Research, Journal Year: 2025, Volume and Issue: Volume 18, P. 4335 - 4357

Published: March 1, 2025

Monoclonal antibodies (mAbs) have transformed cancer treatment by providing highly targeted and effective therapies that specifically attack cells, thus reducing the likelihood of adverse events (AEs) in patients. mAbs exert their action through various mechanisms, such as receptor blockade, antibody-dependent cellular cytotoxicity (ADCC), complement-dependent (CDC), inhibition immune checkpoints (eg, PD-1, PD-L1, CTLA-4). These led to significant improvements several cancers, including HER2-positive breast cancer, non-small cell lung (NSCLC), melanoma. The efficacy mAb therapy is influenced intrinsic extrinsic factors, environmental exposures, psychosocial infection status, ways life, tumor microenvironment (TME), all which can impact responses outcomes. Notably, therapeutic benefits are often accompanied immune-related AEs (irAEs), vary from mild severe affect multiple organ systems. dual nature mAbs-stimulating antitumor while also inducing side effects-presents a notable challenge clinical practice. This review highlights importance proactive strategies for managing irAEs, early detection, corticosteroid use, immunosuppressive treatments, urgent need reliable predictive biomarkers improve Advancements prevention, prediction, management irAEs essential enhance safety effectiveness mAb-based therapies, ultimately aiming patient

Language: Английский

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Combination therapy with oncolytic viruses for lung cancer treatment

Frontiers in Oncology, Journal Year: 2025, Volume and Issue: 15

Published: April 3, 2025

Lung cancer is the leading cause of cancer-related death globally. Despite various treatment options, adverse reactions and resistance limit their clinical application efficacy, therefore, new effective options are still needed. Oncolytic viruses (OVs) a anti-cancer option. With powerful anti-tumor effect, OVs gradually being applied to solid tumor. In practice, we have found that in patients with NSCLC SCLC, combined immune checkpoint inhibitors (ICI) make tumor poor response immunotherapy become sensitive. Furthermore, studies shown chemotherapy, radiation therapy, other approaches (such as anti-pd1 drugs) synergistic effects. These suggest therapy may bring hope for lung patients. This article will review current status prospect combination field summarizes mechanism action.

Language: Английский

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Discovery of a novel 4-pyridyl SLC-0111 analog targeting tumor-associated carbonic anhydrase isoform IX through tail-based design approach with potent anticancer activity

Frontiers in Chemistry, Journal Year: 2025, Volume and Issue: 13

Published: April 4, 2025

Introduction: Carbonic anhydrase IX (CA IX) is a tumor-associated enzyme involved in cancer progression and survival. Targeting CA with selective inhibitors like SLC-0111 has shown therapeutic potential. This study aimed to develop novel 4-pyridyl analog ( Pyr ) of enhanced anticancer activity. Methods: was synthesized using tail-based design characterized by NMR. Its cytotoxicity tested against normal cell lines. inhibition, cycle effects, apoptosis induction, protein expression changes were evaluated. Molecular docking ADMET predictions assessed binding drug-like properties. Results Discussion: showed toward cells potent inhibition. It induced G0/G1 arrest, apoptosis, modulated p53, Bax, Bcl-2 levels. Docking confirmed strong binding, analysis indicated good oral bioavailability. These results support as promising candidate.

Language: Английский

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