Unraveling UPR-Mediated Intercellular Crosstalk: Implications for Immunotherapy Resistance Mechanisms

Cancer Letters, Journal Year: 2025, Volume and Issue: unknown, P. 217613 - 217613

Published: March 1, 2025

Language: Английский

---

Antigen escape in CAR-T cell therapy: Mechanisms and overcoming strategies

Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 178, P. 117252 - 117252

Published: Aug. 3, 2024

Chimeric antigen receptor T (CAR-T) cell therapy has shown promise in treating hematological malignancies and certain solid tumors. However, its efficacy is often hindered by negative relapses resulting from escape. This review firstly elucidates the mechanisms underlying escape during CAR-T therapy, including enrichment of pre-existing target-negative tumor clones, gene mutations or alternative splicing, deficits processing, redistribution, lineage switch, epitope masking, trogocytosis-mediated loss. Furthermore, we summarize various strategies to overcome escape, evaluate their advantages limitations, propose future research directions. Thus, aim provide valuable insights enhance effectiveness therapy.

Language: Английский

---

Predictive Biomarkers and Resistance Mechanisms of Checkpoint Inhibitors in Malignant Solid Tumors

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(17), P. 9659 - 9659

Published: Sept. 6, 2024

Predictive biomarkers for immune checkpoint inhibitors (ICIs) in solid tumors such as melanoma, hepatocellular carcinoma (HCC), colorectal cancer (CRC), non-small cell lung (NSCLC), endometrial carcinoma, renal (RCC), or urothelial (UC) include programmed death ligand 1 (PD-L1) expression, tumor mutational burden (TMB), defective deoxyribonucleic acid (DNA) mismatch repair (dMMR), microsatellite instability (MSI), and the microenvironment (TME). Over past decade, several types of ICIs, including cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibitors, anti-programmed (PD-1) antibodies, anti-lymphocyte activation gene-3 (LAG-3) antibodies have been studied approved by Food Drug Administration (FDA), with ongoing research on others. Recent studies highlight critical role gut microbiome influencing a positive therapeutic response to emphasizing importance modeling factors that can maintain healthy microbiome. However, resistance mechanisms emerge, increased expression alternative checkpoints, T-cell immunoglobulin (Ig), mucin domain-containing 3 (TIM-3), LAG-3, impaired antigen presentation, alterations TME. This review aims synthesize data regarding interactions between microbiota immunotherapy (IT). Understanding these is essential optimizing ICI therapy developing effective combination strategies.

Language: Английский

---

Advanced Therapeutic Approaches for Metastatic Ovarian Cancer

Cancers, Journal Year: 2025, Volume and Issue: 17(5), P. 788 - 788

Published: Feb. 25, 2025

Ovarian cancer is the fifth leading cause of cancer-related death among women, which one most common gynecological cancers worldwide. Although several cytoreductive surgeries and chemotherapies have been attempted to address ovarian cancer, disease still shows poor prognosis survival rates due prevalent metastasis. Peritoneal metastasis recognized as primary route metastatic progression in cancer. It causes severe symptoms patients, but it generally difficult detect at an early stage. Current anti-cancer therapy insufficient completely treat its high recurrence resistance. Therefore, developing strategies for treating requires a deeper understanding tumor microenvironment (TME) identification effective therapeutic targets through precision oncology. Given that various signaling pathways, including TGF-β, NF-κB, PI3K/AKT/mTOR influence progression, their activity significance can vary depending on type. In these pathways are particularly important, they not only drive also impact TME, contributes potential. The TME plays critical role driving features altered immunologic interactions. Recent advances focused targeting distinct improve treatment outcomes. Deciphering complex interaction between immune populations contributing provides opportunity enhance efficacy. Hereby, this review highlights mechanisms immunological interactions understand improved immunotherapy against

Language: Английский

---

Leveraging HER2-targeted Biparatopic Antibodies in Solid Tumors

Pharmacological Research, Journal Year: 2025, Volume and Issue: 214, P. 107687 - 107687

Published: March 5, 2025

Biparatopic antibodies (bpAbs), which target non-overlapping epitopes on the same antigen, offer unique mechanisms of action and therapeutic applications that surpass those conventional monospecific antibodies. These distinctive properties have positioned bpAbs as effective agents in treatment cancer infectious diseases, especially cases where current treatments face limitations. Among these, HER2-targeted shown significant improvements survival outcomes for patients with solid tumors depend HER2 signaling. However, a comprehensive understanding their clinical impact, action, limitations use remains lacking. Here, we review contrast performance well-established use, focus associated limitations, potential combination strategies. We also highlight emerging investigational bpAbs-based promise HER2-positive cancers. advancements may lead to enhanced options potentially broaden scope therapy.

Language: Английский

---

Functional tumor-derived exosomes in NSCLC progression and clinical implications

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

Published: March 19, 2025

Non-small cell lung cancer (NSCLC) accounts for approximately 85% of all cases and remains one the leading causes cancer-related mortality worldwide. The high rate is primarily driven by delayed diagnosis, rapid metastasis, frequent recurrence. Tumor-derived exosomes (TEXs) have emerged as critical mediators in NSCLC progression, offering valuable insights into tumor microenvironment. Exosomes are small membrane vesicles that facilitate intercellular communication transport bioactive molecules, including proteins, RNAs, DNAs, thereby reflecting genetic complexity tumors. These play a key role promoting epithelial-mesenchymal transition (EMT), neovascularization, drug resistance, immune evasion, which pivotal development NSCLC. This review explores diverse roles TEXs focusing on their involvement pre-metastatic niche formation, tissue modulation. Specifically, we discuss exosome-associated RNAs proteins NSCLC, contribute to growth metastasis. Furthermore, explore potential biomarkers emphasizing application prognosis, prediction resistance targeted therapies immunotherapies.

Language: Английский

---

Rational Design of Single‐Atom Nanozymes for Combination Cancer Immunotherapy

Advanced Functional Materials, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 21, 2025

Abstract Remodeling of the tumor immune microenvironment and enhancement antitumor responses are necessary to overcome immunotherapy resistance in tumors. However, heterogeneity complexity evasion mechanisms pose significant therapeutic challenges. Nanozymes exhibit enzyme‐like characteristics unique nanomaterial properties, showing potential for therapy. design effective nanozymes remains complex, inefficient, functionally limited. Therefore, this study, a novel strategy combining rationally designed single‐atom (SAzymes) with checkpoint blockade (ICB) therapy is established. Molybdenum SAzymes supported on graphitic carbon nitride (Mo SAs) constructed using 25 transition metal candidates from 4th 6th periods based high‐throughput calculations optimal piezoelectric‐enhanced multienzyme‐like activities. Upon activation by ultrasound, Mo SAs exerted potent effects against ICB‐resistant tumors remodeled inducing immunogenic cell death, alleviating hypoxia, modulating chemokine expression Combination anti‐programmed death protein‐1 antibodies further enhanced their efficacy, highlighting treat

Language: Английский

---

Current status and future prospects of molecular imaging in targeting the tumor immune microenvironment

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

Published: Jan. 22, 2025

Molecular imaging technologies have significantly transformed cancer research and clinical practice, offering valuable tools for visualizing understanding the complex tumor immune microenvironment. These allow non-invasive examination of key components within microenvironment, including cells, cytokines, stromal providing crucial insights into biology treatment responses. This paper reviews latest advancements in molecular imaging, with a focus on its applications assessing interactions Additionally, challenges faced by are discussed, such as need highly sensitive specific agents, issues data integration, difficulties translation. The future outlook emphasizes potential to enhance personalized through integration artificial intelligence development novel probes. Addressing these is essential fully realizing improving diagnosis, treatment, patient outcomes.

Language: Английский

---

Immune landscape and novel therapeutic targets of epidermal growth factor receptor and anaplastic lymphoma kinase wild type never-smoker lung adenocarcinoma

Lung Cancer, Journal Year: 2025, Volume and Issue: 201, P. 108448 - 108448

Published: Feb. 15, 2025

Language: Английский

---

Microbiota-Derived L-SeMet Potentiates CD8+ T Cell Effector Functions and Facilitates Anti-Tumor Responses

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(6), P. 2511 - 2511

Published: March 11, 2025

Extensive studies have shown that gut microbiota-derived metabolites can enhance the antitumor efficacy of immunotherapy by modulating host immune responses. However, more comprehensive spectrum such and their mechanisms remain unclear. In this study, we demonstrated L-selenomethionine (L-SeMet), a microbial metabolite, acts as positive regulator immunotherapy. Through screening repository metabolites, identified L-SeMet effectively effector function CD8+ T cells. Furthermore, intragastric administration in mice significantly suppressed growth subcutaneous MC38 tumors. Mechanistically, enhances cell receptor (TCR) signaling promoting LCK phosphorylation. Collectively, our findings reveal metabolite inhibits colorectal tumor potentiating functions, providing potential therapeutic strategy for cancer treatment.

Language: Английский

---