Anti-TGF-β/PD-L1 bispecific antibody synergizes with radiotherapy to enhance antitumor immunity and mitigate radiation-induced pulmonary fibrosis

Journal of Hematology & Oncology, Journal Year: 2025, Volume and Issue: 18(1)

Published: March 5, 2025

Despite the success of immune checkpoint inhibitors (ICIs) in multiple malignant tumors, a significant proportion patients remain unresponsive to treatment. Radiotherapy (RT) elicits immunogenic antitumor responses but concurrently activates several evasion mechanisms. Our earlier research demonstrated efficacy YM101, an anti-TGF-β/PD-L1 bispecific antibody, stroma-rich tumors. Nevertheless, YM101 has reduced effectiveness non-inflamed tumors characterized by poor cell infiltration. This study investigated potential synergy between RT and overcoming immunotherapy resistance mitigating RT-induced pulmonary fibrosis. The activity survival outcomes plus treatment vivo were explored murine tumor models. Furthermore, inhibition metastases was assessed metastasis model. impact on dendritic (DC) maturation quantified flow cytometry, whereas cytokine chemokine secretions measured ELISA. To comprehensively characterize changes microenvironment, we utilized combination methods, including IHC staining, multiplex inmunofluorecence RNA sequencing. Additionally, evaluated significantly inhibited growth, prolonged compared with monotherapies promoted DC dose-dependent manner increased proinflammatory cytokines. Mechanistically, simultaneously infiltration activation intratumoral DCs tumor-infiltrating lymphocytes reshaped microenvironment landscape. Notably, attenuated both peritumoral fibrosis findings suggest that combined enhances immunity overcomes preclinical models, while showing therapy demonstrates promise ICI resistance, potentially sparing normal tissue, thereby providing strong rationale for further clinical investigations.

Language: Английский

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Remodeling the Tumor Immune Microenvironment through Hydrogel Encapsulated G-Rh2 In Situ Vaccine and Systemic Immunotherapy

Materials Today Bio, Journal Year: 2024, Volume and Issue: 29, P. 101281 - 101281

Published: Sept. 28, 2024

Language: Английский

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Role of Radiomics-based Multiomics Panel in the Microenvironment and Prognosis of Hepatocellular Carcinoma

Academic Radiology, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Language: Английский

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m6A epitranscriptomic modification in hepatocellular carcinoma: implications for the tumor microenvironment and immunotherapy

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

Published: Feb. 17, 2025

Hepatocellular carcinoma (HCC) is the most prevalent primary liver malignancy and a leading cause of cancer-related deaths globally. The asymptomatic progression early-stage HCC often results in diagnosis at advanced stages, significantly limiting therapeutic options worsening prognosis. Immunotherapy, with immune checkpoint inhibitors (ICIs) forefront, has revolutionized treatment. Nevertheless, tumor heterogeneity, evasion, presence immunosuppressive components within microenvironment (TIME) continue to compromise its efficacy. Furthermore, resistance or non-responsiveness ICIs some patients underscores urgent need unravel complexities TIME design innovative strategies that enhance immunotherapeutic outcomes. Emerging evidence revealed pivotal role N6-methyladenosine (m6A), prominent RNA methylation modification, shaping HCC. By regulating stability translation, m6A influences immune-related factors, including cytokines molecules. This modification governs PD-L1 expression, facilitating escape contributing against ICIs. Advances this field have also identified m6A-related regulators as promising biomarkers for predicting immunotherapy response potential targets optimizing treatment review examines regulatory mechanisms HCC, focus on impact cells cytokine dynamics. It explores targeting pathways improve efficacy outlines emerging directions future research. These insights aim provide foundation developing novel overcome advance

Language: Английский

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The Emerging Role of Histotripsy in Liver Cancer Treatment: A Scoping Review

Cancers, Journal Year: 2025, Volume and Issue: 17(6), P. 915 - 915

Published: March 7, 2025

Background/Objective: Hepatocellular carcinoma (HCC) is an aggressive disease that known to be resistant conventional chemotherapy and radiotherapy. While surgical resection transarterial therapy can improve overall survival, the biological aspects of HCC contribute complexity its management limit effectiveness current treatment options. The purpose this scoping review identify limitations currently available therapies for explore emerging role histotripsy could play in addressing these limitations, with intent informing direction future research clinical management. Methods: PRISMA checklist reviews was followed structure review, a systematic search conducted following online databases: PubMed/MEDLINE (National Library Medicine), Embase (Elsevier), Scopus (Elsevier). Results: evidence supports offers several key advantages address strategies HCC. Clinical trials have highlighted ability technology destroy solid tumors induce remission minimal side effects. In addition, preclinical studies point potent immunostimulatory effects histotripsy, including induction abscopal This poses significant promise treating tumor metastasis as well improving regimens by combining immunotherapy. Future should aim overcome enhance outcomes patients. examines existing treatments HCC, emphasizing promising potential immunotherapy target metastatic advanced stages disease.

Language: Английский

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The epigenetic basis of hepatocellular carcinoma – mechanisms and potential directions for biomarkers and therapeutics

British Journal of Cancer, Journal Year: 2025, Volume and Issue: unknown

Published: March 8, 2025

Abstract Hepatocellular carcinoma (HCC) is the sixth leading cancer worldwide and has complex pathogenesis due to its heterogeneity, along with poor prognoses. Diagnosis often late as current screening methods have limited sensitivity for early HCC. Moreover, treatment regimens intermediate-to-advanced HCC high resistance rates, no robust predictive biomarkers, survival benefits. A deeper understanding of molecular biology may enhance tumor characterization targeting key carcinogenic signatures. The epigenetic landscape includes hallmarks 1) global DNA hypomethylation oncogenes hypermethylation suppressors; 2) histone modifications, altering chromatin accessibility upregulate oncogene expression, and/or suppress suppressor gene expression; 3) genome-wide rearrangement loops facilitating distal enhancer-promoter oncogenic interactions; 4) RNA regulation via translational repression by microRNAs (miRNAs) modifications. Additionally, it useful consider etiology-specific aberrancies, especially in viral hepatitis metabolic dysfunction-associated steatotic liver disease (MASLD), which are main risk factors This article comprehensively explores signatures HCC, highlighting their potential biomarkers therapeutic targets. we examine how patterns integration therapies immunotherapy could advance personalized strategies.

Language: Английский

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Redefining Hepatocellular Carcinoma Treatment: Nanotechnology Meets Tumor Immune Microenvironment

Journal of drug targeting, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 47

Published: March 13, 2025

Hepatocellular carcinoma (HCC) is one of the most lethal malignancies worldwide, characterized by its complex pathogenesis and poor therapeutic outcomes. Despite recent advances in targeted molecular therapies, immune checkpoint inhibitors (ICIs), radiotherapy, conventional chemotherapy, five-year survival rate for this neoplasm remains dismally low. The progress nanotechnology has revolutionized cancer treatment years. These provide unprecedented opportunities to overcome current limitations different modalities. This review provides a comprehensive analysis how interfaces with tumor microenvironment (TIME) HCC can present new frontier interventions HCC. We critically overview latest developments nanoparticle-based delivery systems various drugs also other antitumor agents like thermal therapy radiotherapy. highlight unique ability nanoparticles modulate immunosuppressive (TME) enhance efficacy. Furthermore, we analyze emerging strategies that exploit nanoformulations biological barriers drug bioavailability treatment.

Language: Английский

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Pathogenic Mechanisms of Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD)-Associated Hepatocellular Carcinoma

Cells, Journal Year: 2025, Volume and Issue: 14(6), P. 428 - 428

Published: March 13, 2025

Hepatocellular carcinoma (HCC) is the sixth most common cancer and third leading cause of deaths worldwide. The etiology HCC has now dramatically changed from viral hepatitis to metabolic dysfunction-associated steatotic liver disease (MASLD). main pathogenesis MASLD-related hepatic lipid accumulation hepatocytes, which causes chronic inflammation subsequent progression fibrosis. Chronic generates oxidative stress DNA damage in contribute genomic instability, resulting development HCC. Several molecular pathways are also linked MASLD. In particular, MAPK PI3K-Akt-mTOR upregulated MASLD, promoting survival proliferation cells. addition, MASLD been reported enhance patients with infection. Although there no approved medication for besides resmetirom USA, some preventive strategies onset Sodium-glucose cotransporter-2 (SGLT2) inhibitor, a class medications, exert anti-tumor effects on by regulating reprogramming. Moreover, CD34-positive cell transplantation improves fibrosis intrahepatic angiogenesis supplying various growth factors. Furthermore, exercise through an increase energy consumption as well changes chemokines myokines. this review, we summarize recent progress made pathogenic mechanisms MASLD-associated introduced new therapeutic preventing based

Language: Английский

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Post-translational modifications of immune checkpoints: unlocking new potentials in cancer immunotherapy

Experimental Hematology and Oncology, Journal Year: 2025, Volume and Issue: 14(1)

Published: March 14, 2025

Abstract Immunotherapy targeting immune checkpoints has gained traction across various cancer types in clinical settings due to its notable advantages. Despite this, the overall response rates among patients remain modest, alongside issues of drug resistance and adverse effects. Hence, there is a pressing need enhance checkpoint blockade (ICB) therapies. Post-translational modifications (PTMs) are crucial for protein functionality. Recent research emphasizes their pivotal role regulation, directly impacting expression function these key proteins. This review delves into influence significant PTMs—ubiquitination, phosphorylation, glycosylation—on signaling. By modifications, novel immunotherapeutic strategies have emerged, paving way advancements optimizing therapies future.

Language: Английский

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Integrating Omics: A New Paradigm in the Management of Hepatocellular Carcinoma

Academic Radiology, Journal Year: 2025, Volume and Issue: unknown

Published: March 1, 2025

Language: Английский

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