Emerging Role of Extracellular pH in Tumor Microenvironment as a Therapeutic Target for Cancer Immunotherapy

Cells, Journal Year: 2024, Volume and Issue: 13(22), P. 1924 - 1924

Published: Nov. 20, 2024

Identifying definitive biomarkers that predict clinical response and resistance to immunotherapy remains a critical challenge. One emerging factor is extracellular acidosis in the tumor microenvironment (TME), which significantly impairs immune cell function contributes failure. However, acidic conditions TME disrupt interaction between cancer cells, driving tumor-infiltrating T cells NK into an inactivated, anergic state. Simultaneously, promotes recruitment activation of immunosuppressive such as myeloid-derived suppressor regulatory (Tregs). Notably, acidity enhances exosome release from Tregs, further amplifying immunosuppression. Tumor thus acts "protective shield," neutralizing anti-tumor responses transforming pro-tumor allies. Therefore, targeting lactate metabolism has emerged promising strategy overcome this barrier, with approaches including buffer agents neutralize pH inhibitors block production or transport, thereby restoring efficacy TME. Recent discoveries have identified genes involved (pHe) regulation, presenting new therapeutic targets. Moreover, ongoing research aims elucidate molecular mechanisms acidification develop treatments modulate levels enhance outcomes. Additionally, future studies are crucial validate safety pHe-targeted therapies patients. Thus, review explores regulation pHe its potential role improving immunotherapy.

Language: Английский

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Hepatitis B virus induced cirrhosis and hepatocarcinoma: pathogenesis and therapeutics

Published: Feb. 21, 2025

Hepatitis B virus (HBV) infection is a major risk factor of cirrhosis and hepatocellular carcinoma (HCC) worldwide. Pathogenesis HBV-induced HCC involves viral factors virus-triggered local inflammatory immune responses, the latter leading to progressive fibrosis, carcinogenesis. Antiviral therapeutics suppress HBV replication reduce risks HCC. We discuss current knowledge on pathogenesis HCC, focusing mechanisms emerging antiviral therapeutics.

Language: Английский

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New insights into T cell metabolism in liver cancer: from mechanism to therapy

Cell Death Discovery, Journal Year: 2025, Volume and Issue: 11(1)

Published: March 23, 2025

Abstract Liver cancer is the sixth most common worldwide and third cause of mortality. The development progression liver metastases a multifaceted process involving numerous metabolic pathways. T cells have protective role in defense against cancer, manipulating pathways can alter their antitumor activity. Furthermore, cell nutrition competition lead to dysfunction through various molecular mechanisms. Some nanomaterials drugs improve metabolism promote anti-liver function cells. This review discusses current literature regarding changes targeted therapy for cancer. promise challenges studying target treating are also addressed. Targeting promising approach

Language: Английский

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Current Advancements in Serum Protein Biomarkers for Hepatitis B Virus‐Associated Hepatocyte Remodeling and Hepatocellular Carcinoma

Immunity Inflammation and Disease, Journal Year: 2025, Volume and Issue: 13(4)

Published: April 1, 2025

ABSTRACT Background Hepatitis B virus (HBV)‐related liver cancer is the third most common cause of cancer‐related death globally. Hepatocyte remodeling, also known as hepatocyte transformation and immortalization, hepatocellular carcinoma (HCC), are brought on by persistent inflammation caused HBV in host hepatocytes. One main concerns perspective HBV‐induced remodeling accurately identifying stages to maximize early screening detection. Biological signatures have a significant impact solving this problem. Objective This review article aimed discuss novel serum protein biomarkers for HCC. Methods The information was collected from various peer‐reviewed journals through electronic searches utilizing search engines, including PubMed, Google Scholar, HINARI, Cochrane Library 2017 2024. Keywords included “serum HBV‐HCC,” “blood‐based “viral HBV‐HCC.” Results Recently, been discovered diagnosis, treatment, prognosis hepatic cell HCC proteomic data sets. We discussed recent literature clinical utility diagnosis forecasting HBV‐associated HCC, golgi 73 (GP73), glypican‐3 (GPC3), midkine (MDK), des‐γ‐carboxy‐prothrombin (DCP), von Willebrand factor (vWF), pentraxin 3 (PTX3), pseudouridine synthases 7 (PUSs 7), squamous antigen (SCCA), osteopontin (OPN). Conclusion All these markers exhibit survival HBV‐related patients, proliferation, migration, antiapoptosis, mitogenesis, transformation, angiogenesis HBV‐infected

Language: Английский

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Manipulating the 4-1BB Pathway to Cure HBV

Infectious Diseases & Immunity, Journal Year: 2024, Volume and Issue: 4(4), P. 156 - 157

Published: Aug. 2, 2024

Chronic Hepatitis B Virus (HBV) infection is a major global health issue leading to liver cirrhosis and hepatocellular carcinoma. Currently available treatments have limited efficacy in completely eradicating the virus.[1] The persistence of HBV largely due virus's ability induce dysfunctional state CD8+ T cells. One critical questions why HBV-specific cells become how this dysfunction can be reversed.[2,3] It hypothesized that co-signaling receptors, which play pivotal role cell activation regulation, are key process. Thus, understanding expression modulation these receptors may help identify therapeutic targets restore functionality This approach based on observation traditional immune checkpoint inhibitors, shown success other chronic infections cancers, minimal impact reversing HBV-induced dysfunction,[4] therefore, alternative more effective context. In recent study by Andreata et al,[4] researchers conducted an in-depth analysis receptor address their infection. utilized combination vivo mouse models, bulk single-cell RNA sequencing, various immunological assays upregulated during priming examine potential as targets. While blocking co-inhibitory such PD-1, CTLA-4, LAG-3, showed efficacy, co-stimulatory 4-1BB OX40 significantly restored T-cell function. Specifically, intrahepatically primed consisted progenitor or stem-like (TSL) population two distinct tissue-resident memory (TRM) populations. All three subsets maintained expression, while was TSL. agonism highlighted most promising strategy, capable converting all subpopulations into antiviral effectors. Finally, patients with HBeAg+ CHB infection, rejuvenate provides detailed exploration molecular mechanisms underlying demonstrates activating overcome induced thereby restoring activity. primary findings abovementioned experiments monoclonal lines mice, differ from polyclonal responses observed at stages high heterogeneity quantity functional characteristics, influenced targeted epitopes patient's disease stage. For example, were rarely detected directly ex samples levels viremia. Moreover, Env-specific T-cells found than polymerase- core-specific T-cells.[5,6] responsivity interventions also varies.[7] regulated not only antigen co-stimulation but cytokines (such IL-2) metabolic mechanisms.[8,9] Therefore, further investigation needed understand synergistic interactions among signals, cytokines, factors. conclusion, compelling evidence targeting effectively offers new treatment facilitated development new-generation agonistic drugs improved safety tolerability.[10] addition, presents target for optimizing T-cell-based strategies. Funding work supported National Key Research Development Program China (2022YFA1303600 2023YFC2308100) Natural Science Foundation (82130019). Conflicts Interest None. Editor note: Fu-Sheng Wang editor Infectious Diseases & Immunity. article subject journal's standard procedures, peer review handled independently his research group.

Language: Английский

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Viral Infections and the Glutathione Peroxidase Family: Mechanisms of Disease Development

Antioxidants and Redox Signaling, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 24, 2024

The glutathione peroxidase (GPx) family is recognized for its essential function in maintaining cellular redox balance and countering the overproduction of reactive oxygen species (ROS), a process intricately linked to progression various diseases including those spurred by viral infections. modulation GPx activity viruses presents critical juncture disease pathogenesis, influencing responses trajectory infection-induced diseases.

Language: Английский

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Single-cell analysis reveals distinct immune characteristics of hepatocellular carcinoma in HBV-positive versus HBV-negative cases

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 30, 2024

Abstract Infection with the Hepatitis B virus (HBV) is a key risk factor for Hepatocellular carcinoma (HCC) development and progression. It widely recognized that immunopathological mechanisms are pivotal in developing HBV-related HCC. Nevertheless, specific by which HBV-induced modifications within tumor microenvironment (TME) contribute to HCC pathogenesis still not well understood. Here, we utilized single-cell RNA sequencing analyze compare immune landscapes between HBV-positive HBV-negative We discovered HBV infection significantly modifies cell makeup state, leads suppression exhaustion of T cells TME. Specifically, an increase SLC4A10+ CD8+ IFITM3+ macrophages was observed, along upregulation gene SLC35F1 various subtypes. These findings offer valuable insights into alteration immunological associated infection, suggesting possible targets immunotherapeutic intervention.

Language: Английский

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