Radiotherapy-activated tumor immune microenvironment: Realizing radiotherapy-immunity combination therapy strategies

Nano Today, Journal Year: 2023, Volume and Issue: 53, P. 102042 - 102042

Published: Oct. 31, 2023

Language: Английский

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Compartmentalized spatial profiling of the tumor microenvironment in head and neck squamous cell carcinoma identifies immune checkpoint molecules and tumor necrosis factor receptor superfamily members as biomarkers of response to immunotherapy

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

Published: April 3, 2023

Mucosal head and neck squamous cell carcinoma (HNSCC) are the seventh most common cancer, with approximately 50% of patients living beyond 5 years. Immune checkpoint inhibitors (ICIs) have shown promising results in recurrent or metastatic (R/M) disease, however, only a subset benefit from immunotherapy. Studies implicated tumor microenvironment (TME) HNSCC as major factor therapy response, highlighting need to better understand TME, particularly by spatially resolved means determine cellular molecular components. Here, we employed targeted spatial profiling proteins on cohort pre-treatment tissues R/M disease identify novel biomarkers response within stromal margins. By grouping patient outcome categories into non-response, based Response Evaluation Criteria Solid Tumors (RECIST) show that immune molecules, including PD-L1, B7-H3, VISTA, were differentially expressed. Patient responders possessed significantly higher expression PD-L1 but lower VISTA. Analysis subgroups indicated necrosis receptor (TNFR) superfamily members OX40L, CD27, 4-1BB, CD40, CD95/Fas, associated immunotherapy outcome. CD40 was patient-responders than non responders, while CD95/Fas partial (PR) relative those stable (SD) progressive (PD). Furthermore, found high 4-1BB compartment, not stroma, overall survival (OS) (HR= 0.28, p-adjusted= 0.040). Moreover, regions 0.27, 0.035), CD27 stroma 0.2, p-adjusted=0.032) outcomes. Taken together, this study supports role molecules implicates TNFR key players our HNSCC. Validation these findings prospective is required robustness tissue signatures.

Language: Английский

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The Complex Tumor Microenvironment in Ovarian Cancer: Therapeutic Challenges and Opportunities

Current Oncology, Journal Year: 2024, Volume and Issue: 31(7), P. 3826 - 3844

Published: July 1, 2024

The tumor microenvironment (TME) in ovarian cancer (OC) has much greater complexity than previously understood. In response to aggressive pro-angiogenic stimulus, blood vessels form rapidly and are dysfunctional, resulting poor perfusion, tissue hypoxia, leakiness, which leads increased interstitial fluid pressure (IFP). Decreased perfusion high IFP significantly inhibit the uptake of therapies into tumor. Within TME, there numerous inhibitor cells, such as myeloid-derived suppressor cells (MDSCs), association macrophages (TAMs), regulatory T (Tregs), cancer-associated fibroblasts (CAFs) that secrete numbers immunosuppressive cytokines. This environment is thought contribute lack success immunotherapies immune checkpoint (ICI) treatment. review discusses components TME OC, how these characteristics impede therapeutic efficacy, some strategies alleviate this inhibition.

Language: Английский

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Immune checkpoint inhibitors associated cardiovascular immune-related adverse events

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

Published: Feb. 5, 2024

Immune checkpoint inhibitors (ICIs) are specialized monoclonal antibodies (mAbs) that target immune checkpoints and their ligands, counteracting cancer cell-induced T-cell suppression. Approved ICIs like cytotoxic T-lymphocyte antigen-4 (CTLA-4), programmed death-1 (PD-1), its ligand PD-L1, lymphocyte activation gene-3 (LAG-3) have improved patient outcomes by enhancing anti-tumor responses. However, some patients unresponsive, others experience immune-related adverse events (irAEs), affecting organs the lung, liver, intestine, skin now cardiovascular system. These cardiac irAEs include conditions myocarditis, atherosclerosis, pericarditis, arrhythmias, cardiomyopathy. Ongoing clinical trials investigate promising alternative co-inhibitory receptor targets, including T cell immunoglobulin mucin domain-containing protein 3 (Tim-3) immunoreceptor with ITIM domain (TIGIT). This review delves into mechanisms of approved (CTLA-4, PD-1, LAG-3) upcoming options Tim-3 TIGIT. It explores use in treatment, supported both preclinical data. Additionally, it examines behind toxic irAEs, focusing on ICI-associated myocarditis atherosclerosis. insights vital as continue to revolutionize therapy, offering hope patients, while also necessitating careful monitoring management potential side effects, emerging complications.

Language: Английский

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Current and Future Trends of Colorectal Cancer Treatment: Exploring Advances in Immunotherapy

Cancers, Journal Year: 2024, Volume and Issue: 16(11), P. 1995 - 1995

Published: May 24, 2024

Cancer of the colon and rectum (CRC) has been identified among three most prevalent types cancer cancer-related deaths for both sexes. Even though significant progress in surgical chemotherapeutic techniques markedly improved disease-free overall survival rates contrast to those decades ago, recent years have seen a stagnation these improvements. This underscores need new therapies aiming augment patient outcomes. A number emerging strategies, such as immune checkpoint inhibitors (ICIs) adoptive cell therapy (ACT), exhibited promising outcomes not only preclinical but also clinical settings. Additionally, thorough appreciation underlying biology expanded scope research into potential therapeutic interventions. For instance, pivotal role altered telomere length early CRC carcinogenesis, leading chromosomal instability dysfunction, presents avenue future treatments. Thus, this review explores advancements immunotherapy telomere-targeted therapies, examining synergies how novel treatment modalities intersect potentially enhance each other’s efficacy, paving way advancements.

Language: Английский

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