Exploration of the role of immune cells and cell therapy in hepatocellular carcinoma

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

Published: April 16, 2025

Hepatocellular carcinoma stands as one of the foremost contributors to cancer-associated fatalities globally, and limitations traditional treatment methods have prompted researchers explore new therapeutic options. Recently, cell therapy has emerged a promising approach for HCC, showing significant potential in improving patient outcomes. This review article explores use covering different types, mechanisms behind their effectiveness, recent advancements clinical trials, ongoing challenges. aims provide insightful perspectives future research applications treating HCC by synthesizing current knowledge.

Language: Английский

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A CD8αβ co-receptor modified to contain an intracellular CD28 signaling tail enhances TCR-engineered T cell function independent of solid-tumor-associated co-stimulatory ligands

Research Square (Research Square), Journal Year: 2025, Volume and Issue: unknown

Published: April 21, 2025

Adoptive therapies using T cells genetically modified with cell receptors (TCR)s have shown limited efficacy in the solid tumor setting. Although functional CD4⁺ and CD8⁺ transduced a TCR specific for HLA-A2-restricted melanoma-associated antigen A1 (MAGE-A1, T_{TCR−MA1−CD8αβ}) could be detected post-transfer were safe one patient who subsequently progressed, T_{TCR−MA1−CD8αβ} insufficient to sustain antitumor activity “stress” mouse models. Leveraging obligate co-expression of CD8αβ required engagement expressing TCR, we screened positive co-stimulatory signals tethered intracellular tail CD8β identified that CD28 reduced exhaustion, enhanced infiltration improved murine control. Further modifications domain produced mutant CD8β-CD28 construct conferred superior therapeutic control across Thus, integrating downstream signaling complex can enhance TCR-engineered function, independent tumor-associated ligand expression.

Language: Английский

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Advancing Head and Neck Cancer Therapies: From Conventional Treatments to Emerging Strategies

Biomedicines, Journal Year: 2025, Volume and Issue: 13(5), P. 1046 - 1046

Published: April 25, 2025

Head and neck cancers (HNCs), particularly head squamous cell carcinoma (HNSCC), are among the most aggressive prevalent malignancies of upper aerodigestive tract. As incidence HNCs continues to rise, this cancer type presents a significant public health challenge. Despite conventional treatment options, such as surgery, chemotherapy, radiotherapy, five-year survival rates remain relatively low due resistance these therapies, local recurrence, lymph node metastasis, in some advanced cases also distant metastasis. Consequently, patients with face high mortality risk have reduced quality life side effects chemo- radiotherapy. Furthermore, targeted therapies immunotherapies shown limited effectiveness many cases, issues related accessibility treatments. Therefore, new strategies, those based on combination nanotechnology, being explored improve HNC patients. The proteolysis-targeting chimeras (PROTACs) emerged promising therapeutic approach, though research is still ongoing bring technology into clinical practice. Here, we aim highlight current knowledge focus recent advancements, including nanomedicine PROTAC-based strategies. development advancement novel emerging hold promise for improvement patients’ life.

Language: Английский

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Advances in T Cell-Based Cancer Immunotherapy: From Fundamental Mechanisms to Clinical Prospects

Molecular Pharmaceutics, Journal Year: 2025, Volume and Issue: unknown

Published: May 13, 2025

T cells and their cell receptors (TCRs) play crucial roles in the adaptive immune system's response against pathogens tumors. However, immunosenescence, characterized by declining function quantity with age, significantly impairs antitumor immunity. Recent years have witnessed remarkable progress cell-based cancer treatments, driven a deeper understanding of biology innovative screening technologies. This review comprehensively examines maturation mechanisms, cell-mediated responses, implications thymic involution on diversity prognosis. We discuss recent advances adoptive therapies, including tumor-infiltrating lymphocyte (TIL) therapy, engineered receptor (TCR-T) chimeric antigen (CAR-T) therapy. Notably, we highlight emerging DNA-encoded library technologies mammalian for high-throughput TCR-antigen interactions, which are revolutionizing discovery novel tumor antigens optimization TCR affinity. The also explores strategies to overcome challenges solid microenvironment approaches enhance efficacy As our deepens advances, immunotherapies show increasing promise delivering durable clinical benefits broader patient population.

Language: Английский

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Update: Immunotherapeutic Strategies in HPV-Associated Head and Neck Squamous Cell Carcinoma

Viruses, Journal Year: 2025, Volume and Issue: 17(5), P. 712 - 712

Published: May 16, 2025

The incidence of human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC) has increased substantially over the past three decades, and since 2017, it been recognized in AJCC staging system as distinct from its HPV-negative counterpart. underlying mechanisms HPV-associated carcinogenesis, tumor microenvironment, host immune response represent opportunities for therapeutic development. While anti-PD-1 immunotherapy is now part standard treatment recurrent or metastatic head neck (HNSCC) general, there are no established immunotherapeutic strategies specifically HPV-related HNSCC. In this context, multiple emerging approaches being actively studied—among these vaccines with without anti-PD-(L)1 adjuvants, peptide–HLA-based platforms, adoptive therapies including tumor-infiltrating lymphocytes (TILs), T-cell receptor (TCR) therapy, chimeric antigen (CAR) therapy. Beyond further maturation novel strategies, additional work needed to delineate optimal disease state application (localized versus recurrent/metastatic), well development small molecule inhibitors targeting HPV-specific viral oncogenesis.

Language: Английский

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Strategies for Improving CAR T Cell Persistence in Solid Tumors

Cancers, Journal Year: 2024, Volume and Issue: 16(16), P. 2858 - 2858

Published: Aug. 16, 2024

CAR T cells require optimization to be effective in patients with solid tumors. There are many barriers affecting their ability succeed. One barrier is persistence, as achieve an optimal antitumor response, infused must engraft and persist. This singular variable impacted by a multitude of factors—the cell design, lymphodepletion regimen used, expansion method generate the product, more. Additionally, external agents can utilized augment cells, such addition novel cytokines, pharmaceutical drugs that bolster memory formation, or other during either ex vivo process after infusion support them oppressive tumor microenvironment. review highlights strategies being used optimize persistence well future directions for improving cells.

Language: Английский

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Clinical advances and challenges associated with TCR-T cell therapy for cancer treatment

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

Published: Oct. 8, 2024

Background T cell receptor (TCR)-T therapy is an innovative form of cancer immunotherapy that genetically modifies patients’ cells to target and destroy cells. However, the current status clinical trials TCR-T for treatment remains unclear. This study aimed comprehensively analyze registration related cancer. Methods A comprehensive search was conducted in Trialtrove database all registered by August 1, 2024. Inclusion criteria focused on targeting oncology, excluded observational studies incomplete data. Statistical analysis performed key trial characteristics, with between-group comparisons utilizing chi-square or Fisher’s exact tests. Results Analysis 174 eligible revealed exhibits significant efficacy across various tumor types, particularly refractory hematologic malignancies certain solid tumors. Additionally, combining other immunotherapies enhanced these anti-tumor effects. Conclusion holds substantial promise treatment. Future research should focus optimizing protocols, enhancing efficacy, minimizing prices fully realize potential this therapy.

Language: Английский

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Combined immunotherapy with dendritic cells and cytokine-induced killer cells for solid tumors: a systematic review and meta-analysis of randomized controlled trials

Journal of Translational Medicine, Journal Year: 2024, Volume and Issue: 22(1)

Published: Dec. 20, 2024

Immunotherapy utilizing dendritic cells (DCs) and cytokine-induced killer (CIK) is a promising treatment approach for solid tumors. This systematic review meta-analysis aimed to evaluate the efficacy safety of DC-CIK immunotherapy by assessing overall survival, progression-free response rate, disease control adverse events in relevant randomized controlled trials. The results this analysis will contribute optimizing strategies improving cancer outcomes. adhered PRISMA guidelines. A comprehensive search was conducted on multiple databases RCTs studying combination Inclusion criteria were comparing with therapy reporting OS, PFS, ORR, or DCR. Two authors independently performed study selection data extraction, disagreements resolved through consensus consultation third reviewer. Extracted included characteristics, participant information, interventions, outcomes, quality assessment. Statistical using Review Manager Stata software. Heterogeneity assessed chi-square I-squared statistics. Sensitivity assessment publication bias planned. total 1013 records initially retrieved, after thorough screening process, 13 trials (RCTs) meta-analysis. These studies involved 1443 patients, 730 receiving 713 groups. covered various types, majority mainland China. showed that associated improved survival (OS) (PFS) compared therapy. Furthermore, demonstrated higher rate (ORR) (DCR) non-DC-CIK Adverse reported both groups, fever being more common group bone marrow suppression gastrointestinal reactions group. analyses confirmed stability results, while observed PFS fever. shows tumors, rates rates. Further research needed optimize regimens identify predictive factors.

Language: Английский

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Navigating immunotherapy for ovarian cancer: current landscape and future perspectives

Journal of Cancer Metastasis and Treatment, Journal Year: 2024, Volume and Issue: unknown

Published: June 26, 2024

Ovarian cancer (OC) is the leading cause of death related to gynecologic malignancies, with recurrence occurring frequently despite significant advances in surgical interventions and chemotherapy. Therefore, novel therapies are necessary improve long-term prognosis disease. Immunotherapy holds promise OC treatment by harnessing potential immune system combat neoplastic cells. The effectiveness immunotherapy has been demonstrated numerous cancers subsequently integrated into clinical practice. However, initial preclinical findings suggesting an immunogenic microenvironment OC, checkpoint inhibitors have not shown outcomes studies thus far. Further investigation needed fully understand role immunity develop more effective therapeutic strategies, including combinatorial approaches identification predictive biomarkers for accurate patient selection immunotherapy.

Language: Английский

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Combining iRGD with HuFOLactis enhances antitumor potency by facilitating immune cell infiltration and activation

Human Vaccines & Immunotherapeutics, Journal Year: 2024, Volume and Issue: 20(1)

Published: Aug. 5, 2024

Multiple research studies have demonstrated the efficacy of lactic acid bacteria in boosting both innate and adaptive immune responses. We created a Lactococcus lactis variant that produces modified combination protein with Fms-like tyrosine kinase 3 ligand co-stimulator O × 40 ligand, known as HuFOLactis. The genetically was purposely to activate T cells, NK DC cells laboratory setting. Furthermore, we explored possibility using tumor-penetrating peptide iRGD deliver HuFOLactis-activated hard-to-reach tumor areas. Following brief stimulation HuFOLactis, cell phenotypes functions were assessed flow cytometry. Confocal microscopy employed demonstrate infiltrative cytotoxic capabilities iRGD-modified within spheroids. against tumors xenograft mouse models. HuFOLactis treatment resulted notable activation, by elevated levels CD25, CD69, CD137. Additionally, these activated showed heightened cytokine production enhanced cytotoxicity MKN45 lines. Incorporation modification facilitated infiltration into multicellular spheroids (MCSs). iRGD, anti-PD-1 treatment, effectively halted growth prolonged survival model gastric cancer.

Language: Английский

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