Comprehensive Analysis Identifies THEMIS2 as a Potential Prognostic and Immunological Biomarker in Glioblastoma

Cells, Journal Year: 2025, Volume and Issue: 14(2), P. 66 - 66

Published: Jan. 7, 2025

Glioblastoma (GBM) is a highly aggressive brain tumor characterized by its ability to evade the immune system, hindering efficacy of current immunotherapies. Recent research has highlighted important role immunosuppressive macrophages in microenvironment (TME) driving this evasion. In study, we are first identify THEMIS2 as key regulator tumor-associated macrophage (TAM)-mediated immunosuppression GBM. We found that high expression associated with poor patient outcomes and increased infiltration cells, particularly macrophages. Functional analyses revealed THEMIS2's critical involvement immune-related pathways, including response activation, mononuclear cell differentiation, positive regulation cytokine production. Additionally, single-cell RNA sequencing data demonstrated were phagocytosis, suppression, enhanced growth. These findings suggest could serve both prognostic marker therapeutic target for enhancing anti-tumor immunity

Language: Английский

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Advancements in Melanoma Treatment: A Review of PD-1 Inhibitors, T-VEC, mRNA Vaccines, and Tumor-Infiltrating Lymphocyte Therapy in an Evolving Landscape of Immunotherapy

Journal of Clinical Medicine, Journal Year: 2025, Volume and Issue: 14(4), P. 1200 - 1200

Published: Feb. 12, 2025

Melanoma, an aggressive skin cancer, presents significant therapeutic challenges. Consequently, innovative treatment strategies beyond conventional chemotherapy, radiation, and surgery are actively explored. This review discusses the evolution of immunotherapy in advanced melanoma, highlighting PD-1/PD-L1 inhibitors, mRNA vaccines, Talimogene Laherparepvec (T-VEC), tumor-infiltrating lymphocyte (TIL) therapies. inhibitors such as pembrolizumab nivolumab block immune checkpoints, promoting T-cell cytotoxic activity improving overall survival patients with melanoma. T-VEC, a modified oncolytic herpes virus, promotes systemic anti-tumor response while simultaneously lysing malignant cells. Moderna's mRNA-4157/V940, take advantage malignant-cell-specific neoantigens to amplify adaptive protecting healthy tissue. TIL therapy is form involving ex vivo expansion reinfusion patient's tumor-specific lymphocytes has been shown provide durable tumor control. While these therapies have demonstrated promising clinical outcomes, challenges resistance, high financial burden, limited accessibility pose their widespread use. explores combination PD-L1 or therapy, which aim enhance through synergistic approaches. Further research required optimize combinations, address barriers preventing use, control adverse events.

Language: Английский

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Exploring neuroblastoma’s cellular microenvironment: A novel approach using cellular automata to model Celyvir treatment

Computers in Biology and Medicine, Journal Year: 2025, Volume and Issue: 188, P. 109782 - 109782

Published: Feb. 12, 2025

Language: Английский

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Intratumoral administration of mRNA COVID-19 vaccine delays melanoma growth in mice

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: Feb. 13, 2025

Immunotherapies are effective for cancer treatment but limited in 'cold' tumor microenvironments due to a lack of infiltrating CD8+ T cells, key players the anti-cancer immune response. The onset COVID-19 pandemic sparked widespread use mRNA-formulated vaccines and is well documented that vaccination induces Th1-skewed Here, we evaluated effects an intratumoral injection mRNA vaccine subcutaneous melanoma mouse models. Tumor growth survival studies following single showed significant suppression prolonged established B16F10 tumor-bearing mice. resulted increase cell infiltration into microenvironment, as observed using intravital imaging flow cytometry. Further was achieved additional treatments. Combination administration with checkpoint therapies demonstrated enhanced effects, further delaying improving time This study demonstrates may be used adjuvants immunotherapies.

Language: Английский

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Is it time to revisit the significance of PD-L1 expression in assisting our treatment decisions?

Immunotherapy, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 5

Published: March 21, 2025

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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B7H3 in Gastrointestinal Tumors: Role in Immune Modulation and Cancer Progression: A Review of the Literature

Cells, Journal Year: 2025, Volume and Issue: 14(7), P. 530 - 530

Published: April 2, 2025

B7-H3 (CD276), a member of the B7 immune checkpoint family, plays critical role in modulating responses and has emerged as promising target cancer therapy. It is highly expressed various malignancies, where it promotes tumor evasion from T cell surveillance contributes to progression, metastasis, therapeutic resistance, showing correlation with poor prognosis patients. Although its receptors were not fully identified, signaling involves key intracellular pathways, including JAK/STAT, NF-κB, PI3K/Akt, MAPK, driving processes crucial for supporting growth such proliferation, invasion, apoptosis inhibition. Beyond modulation, influences metabolism, angiogenesis, epithelial-to-mesenchymal transition, further exacerbating aggressiveness. The development B7-H3-targeting therapies, monoclonal antibodies, antibody–drug conjugates, CAR-T cells, offers avenues treatment. This review provides an up-to-date summary B7H3 mechanisms action, putative receptors, ongoing clinical trials evaluating therapies targeting B7H3, focusing on molecule’s gastrointestinal tumors.

Language: Английский

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Whole-Body Physiologically Based Pharmacokinetic Modeling Framework for Tissue Target Engagement of CD3 Bispecific Antibodies

Pharmaceutics, Journal Year: 2025, Volume and Issue: 17(4), P. 500 - 500

Published: April 9, 2025

Background: T-cell-engaging bispecific (TCB) antibodies represent a promising therapy that utilizes T-cells to eliminate cancer cells independently of the major histocompatibility complex. Despite their success in hematologic cancers, challenges such as cytokine release syndrome (CRS), off-tumor toxicity, and resistance limit efficacy solid tumors. Optimizing biodistribution is key overcoming these challenges. Methods: A physiologically based pharmacokinetic (PBPK) model was developed incorporates T-cell transmigration, retention, receptor binding, turnover, cellular engagement. Preclinical data were modeled using two TCB formats: one lacking tumor target binding another with arm each varying CD3 affinities transgenic tumor-bearing mouse model. Results: The PBPK successfully described distribution activated various formats. It accurately predicted preclinical patterns, demonstrating higher affinity leads faster clearance from blood increased accumulation T-cell-rich organs, often reducing exposure. Simulations HER2-CD3 doses (0.1 µg 100 mg) revealed monotonic increases synapse AUC within tumor. bell-shaped dose-Cmax relationship for formation observed, Tmax delayed at doses. Blood PK reasonable surrogate low but less predictive Conclusions: We whole-body simulate molecules. insights this provide comprehensive understanding factors affecting PK, formation, activity, aiding dose optimization design effective therapeutic strategies.

Language: Английский

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Immunotherapy for Renal Cell Carcinoma—What More is to Come?

Targeted Oncology, Journal Year: 2025, Volume and Issue: unknown

Published: April 10, 2025

Language: Английский

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From Defense to Disease: How the Immune System Fuels Epithelial–Mesenchymal Transition in Ovarian Cancer

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(9), P. 4041 - 4041

Published: April 24, 2025

Ovarian cancer is one of the most deadly gynecological cancers, with over 300 thousand new cases per year, which are diagnosed in advanced stages. The limited availability effective biomarkers and lack characteristic symptoms make early diagnosis difficult, resulting a five-year survival rate 30–40%. Mutations BRCA1 BRCA2 genes abnormalities signaling pathways such as PI3K/AKT TP53 play key role progression ovarian cancer. immune system, can act against tumors, often supports tumor development microenvironment through immunoevasion, influenced by cytokines IL-6, IL-10, TGF-β. Epithelial-to-mesenchymal transition (EMT) allows cells to acquire mesenchymal characteristics, increasing their invasiveness metastatic capacity. Immunological factors, including pro-inflammatory signals from regulate EMT process. This review aims present progression, its interactions potential therapeutic targets. Modulation response inhibition may constitute basis for personalized therapies, opens possibilities improving prognosis efficacy treatment patients

Language: Английский

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