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Background: Recent advancements in combination therapy for unresectable hepatocellular carcinoma (uHCC) have shown promise, but reliable serological prognostic indicators are currently lacking for patients undergoing triple combination therapy of stereotactic body radiation therapy (SBRT), immunotherapy, and targeted therapy. We aimed to investigate the prognostic significance of early alpha fetoprotein (AFP) and des-gamma-carboxy prothrombin (DCP) responses in these patients.
Methods: This retrospective research included 115 uHCC patients treated with SBRT in combination with immunotherapy and targeted therapy (triple therapy) at our institution from April 2021 to December 2022. Participants were categorized into high AFP and high DCP cohorts based on baseline levels. AFP and DCP responses were defined as decreases from baseline of over 50% and 70%, respectively, according to ROC curve analysis. Differences in overall survival (OS), progression-free survival (PFS), and objective response rate (ORR) were assessed between the tumor biomarker response and non-response groups.
Results: Multivariate analysis indicated that AFP or DCP response at 6-8 weeks post-therapy significantly influenced ORR (high AFP cohort: odds ratio [OR] 5.50, 95% CI 2.04-14.83, p=0.001; high DCP cohort: OR 7.99, 95%CI 2.82-22.60, p<0.001). The median PFS was notably longer in tumor biomarker response groups (high AFP cohort: 13.7 vs 6.2 months, hazard ratio [HR] 0.36, 95% CI 0.20-0.62, p<0.001; high DCP cohort: 15.6 vs 9.3 months, HR 0.44, 95% CI 0.26-0.74, p=0.002). AFP or DCP response was associated with prolonged OS (high AFP cohort: not reached vs. 21.9 months, HR 0.47, 95% CI 0.22-0.99, p=0.047; high DCP cohort: not reached vs. 20.6 months, HR 0.35, 95% CI 0.14-0.86, p=0.022).
Conclusion: AFP or DCP response at 6-8 weeks post-therapy predicts better oncological outcomes in patients with uHCC treated with triple therapy.
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http://dx.doi.org/10.3389/fimmu.2024.1508028 | DOI Listing |
Cancer Immunol Immunother
September 2025
Department of Gastric Surgery, Chinese Academy of Sciences, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Hangzhou, 310022, Zhejiang, China.
Objectives: To evaluate the efficacy of combining PD-1 inhibitors with chemotherapy in conversion therapy for patients with stage IV gastric cancer and to determine the populations most likely to benefit from this regimen.
Methods: Data from patients with stage IV gastric cancer who received conversion therapy with PD-1 inhibitors combined with chemotherapy between January 2018 and December 2022 at multiple centers were retrospectively reviewed. Patients who underwent conversion surgery were categorized into a surgery group, while those who did not were placed into a palliative group.
Cell Mol Immunol
September 2025
School of Chinese Medicine, the University of Hong Kong, Hong Kong SAR, China.
Type I interferon (IFN-I) is highly prevalent in autoimmune disorders and is intricately involved in disease pathogenesis, including Sjögren's disease (SjD), also known as Sjögren's syndrome. Although the T follicular helper (Tfh) cell response has been shown to drive SjD development in a mouse model of experimental Sjögren's syndrome (ESS), the connection between IFN-I and the Tfh cell response remains unclear. As the activation of stimulator of interferon genes (STING) induces IFN-I production, we first demonstrated that mice deficient in STING or IFN-I signaling presented diminished Tfh cells and were completely resistant to ESS development.
View Article and Find Full Text PDFOncogene
September 2025
Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Pancreatic cancer is a highly aggressive malignancy with a dismal prognosis, characterized by a complex tumor microenvironment that promotes immunosuppression and limits the efficacy of immune checkpoint blockade (ICB) therapy. Fibroblast activation protein (FAP) is overexpressed in the tumor stroma and represents a promising target for therapeutic intervention. Here, we developed a novel antibody-drug conjugate (ADC) targeting FAP, and investigated its anti-tumor activity and ability to enhance ICB efficacy in pancreatic cancer.
View Article and Find Full Text PDFPharmacoepidemiol Drug Saf
September 2025
Sanofi, Cambridge, Massachusetts, USA.
Purpose: Given the increased likelihood for individuals with severe asthma to experience comorbidities, disease complications, emergency room visits, and hospitalizations, the ability to stratify asthma populations on severity is often important. Although pharmacoepidemiologic studies using administrative healthcare databases sometimes categorize asthma severity, there is no consensus on an approach.
Methods: Individuals with asthma (≥ 2 ICD-10-CM diagnosis codes J45) aged ≥ 6 years were identified in Optum's de-identified Clinformatics Data Mart Database between January 2017 and November 2023.
Trends Immunol
September 2025
Department of Life Science, University of Seoul, Seoul, Republic of Korea. Electronic address:
Despite an effective combination of antiretroviral therapy, HIV persists as a lifelong infection and global health threat. The human host equips restriction factors and interferon (IFN)-stimulated genes that target every step of the viral life cycle. However, HIV-1 has evolved a coordinated immune evasion strategy using a limited set of accessory proteins with distinct antagonistic functions.
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