Adjuvant sintilimab in resected high-risk hepatocellular carcinoma: a randomized, controlled, phase 2 trial

Nature Medicine, Journal Year: 2024, Volume and Issue: 30(3), P. 708 - 715

Published: Jan. 19, 2024

Language: Английский

---

Targeting SRSF10 might inhibit M2 macrophage polarization and potentiate anti‐PD‐1 therapy in hepatocellular carcinoma

Cancer Communications, Journal Year: 2024, Volume and Issue: 44(11), P. 1231 - 1260

Published: Sept. 2, 2024

Abstract Background The efficacy of immune checkpoint blockade therapy in patients with hepatocellular carcinoma (HCC) remains poor. Although serine‐ and arginine‐rich splicing factor (SRSF) family members play crucial roles tumors, their impact on tumor immunology unclear. This study aimed to elucidate the role SRSF10 HCC immunotherapy. Methods To identify key genes associated immunotherapy resistance, we conducted single‐nuclear RNA sequencing, multiplex immunofluorescence, Cancer Genome Atlas Gene Expression Omnibus database analyses. We investigated biological functions evasion using vitro co‐culture systems, flow cytometry, various tumor‐bearing mouse models, patient‐derived organotypic spheroids. Results was upregulated tumors poor prognosis. Moreover, positively regulated lactate production, SRSF10/glycolysis/ histone H3 lysine 18 lactylation (H3K18la) formed a positive feedback loop cells. Increased levels promoted M2 macrophage polarization, thereby inhibiting CD8 + T cell activity. Mechanistically, interacted 3′‐untranslated region MYB , enhancing stability, subsequently upregulating glycolysis‐related enzymes including glucose transporter 1 ( GLUT1 ), hexokinase HK1 dehydrogenase A LDHA resulting elevated intracellular extracellular levels. Lactate accumulation induced lactylation, which further expression. Additionally, produced by H3K18la site upon transport into macrophages, activating transcription pro‐tumor turn, inhibited enrichment cells proportion interferon‐γ microenvironment (TME), thus creating an immunosuppressive TME. Clinically, could serve as biomarker for assessing resistance solid tumors. Pharmacological targeting selective inhibitor 1C8 enhanced programmed death (PD‐1) monoclonal antibodies (mAbs) both murine human preclinical models. Conclusions SRSF10/MYB/glycolysis/lactate axis is critical triggering anti‐PD‐1 resistance. Inhibiting may overcome tolerance HCC.

Language: Английский

---

FOXM1 promotes malignant biological behavior and metabolic reprogramming by targeting SPINK1 in hepatocellular carcinoma and affecting the p53 pathway

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, Journal Year: 2025, Volume and Issue: unknown, P. 167673 - 167673

Published: Jan. 1, 2025

Language: Английский

---

Lenvatinib, sintilimab plus transarterial chemoembolization for advanced stage hepatocellular carcinoma: A phase II study

Liver International, Journal Year: 2024, Volume and Issue: 44(4), P. 920 - 930

Published: Jan. 30, 2024

Abstract Background & Aims Our retrospective study has suggested encouraging outcomes of lenvatinib combined with PD‐1 inhibitor and transarterial chemoembolization (TACE) on advanced hepatocellular carcinoma (HCC). This phase II trial was conducted to prospectively investigate the efficacy safety lenvatinib, sintilimab (a inhibitor) plus TACE (Len‐Sin‐TACE) in patients stage HCC. Methods a single‐arm trial. Patients BCLC C HCC were recruited. They received (bodyweight ≥60 kg, 12 mg; bodyweight <60 8 mg) orally once daily, (200 intravenously every 3 weeks, demand TACE. The primary endpoint progression‐free survival (PFS) per mRECIST. Results Thirty enrolled. met median PFS 8.0 (95% confidence interval [CI]: 6.1–9.8) months mRECIST, which same as that RECIST 1.1. objective response rate 60.0% mRECIST 30.0% disease control 86.7% mRECIST/RECIST duration 7.4 CI: 6.6–8.2) ( n = 18) 4.3 4.0–4.6) 1.1 9). overall 18.4 14.5–22.3) months. Treatment‐related adverse events (TRAEs) occurred 28 (93.3%) grade TRAEs observed (40.0%). There no 4/5 TRAEs. Conclusions Len‐Sin‐TACE showed promising antitumour activities manageable profile preliminary results need be further evaluated III randomized trials.

Language: Английский

---

Immunotherapy vs Best Supportive Care for Patients With Hepatocellular Cancer With Child-Pugh B Dysfunction

JAMA Oncology, Journal Year: 2024, Volume and Issue: 10(9), P. 1253 - 1253

Published: July 18, 2024

Whether patients with Child-Pugh class B (CP-B) cancer unresectable hepatocellular carcinoma (uHCC) benefit from active anticancer treatment vs best supportive care (BSC) is debated.

Language: Английский

---

Tumor-infiltrating T lymphocytes: A promising immunotherapeutic target for preventing immune escape in cholangiocarcinoma

Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 177, P. 117080 - 117080

Published: July 6, 2024

Cholangiocarcinoma (CCA) is becoming more common and deadly worldwide. Tumor-infiltrating T cell subtypes make distinct contributions to the immune system; collectively, they constitute a significant portion of tumor microenvironment (TME) in CCA. By secreting cytokines other chemicals, regulatory cells (Tregs) decrease activated responses, acting as immunosuppressors. Reduced CD8

Language: Английский

---

Editorial: High Baseline ALT Level Confers Risk of Hepatic Adverse Events During Immune Checkpoint Inhibitors Treatment—A Call for Caution

Alimentary Pharmacology & Therapeutics, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 7, 2025

The discovery of immune checkpoint inhibitors (ICIs) is a major breakthrough for the treatment patients with variety malignancies, including hepatocellular carcinoma (HCC). Evidence has accumulated that ICIs can induce remission and prolong survival advanced malignancies. Hence, ICI-based regimens are recommended as first-line systemic therapy [1, 2]. However, increased application ICI treatments raised concerns regarding their hepatotoxicity, especially in HCC [3]. It remains unclear whether ICI-induced hepatic adverse events (AEs) more common than other cancer types. Moreover, risk factors AEs during non-HCC respectively, need to be identified. Recently, Hung et al. compared incidence those malignancies retrospective cohort hepatitis B virus (HBV)-endemic areas [4]. They showed had higher flare HBV reactivation (HBVr) whereas incidences immune-related (irHepatitis) were similar two groups patients. Furthermore, they identified baseline alanine aminotransferase (ALT) concentration exceeding 40 U/L was an independent factor grade 3 or irHepatitis. These results demonstrate susceptibility treatment-associated highlight importance monitoring ALT concentrations nucleos(t)ide analogue (NUC) prophylaxis before initiation treatment. authors did not propose practical model on basis predict irHepatitis large proportion have liver cirrhosis thus impaired function elevated levels. Therefore, hardly used clinical decision-making severe which caused by pre-existing diseases. In contrast, suitable cutoff value would support evaluating probability treatment-induced AEs. Predictive models been developed immunotherapy-related but lacking [5-7]. researchers found increases HBVr this accompanied antiviral [4, 8]. according another study authors, also restore exhausted T-cell immunity, may accelerate loss surface antigen (HBsAg) thereby contribute functional cure chronic [9]. effect anti-HBV immunity appears double-edged, depending balance status NUC employed (Figure 1). Nevertheless, it DNA load HBsAg determine immunity. Thus, mechanisms underpinning double-edged role infection further delineated. Ze-Hua Zhao: writing – original draft. Yu-Chen Fan: conceptualization, review editing, funding acquisition. declare no conflicts interest. This article linked al papers. To view these articles, visit https://doi.org/10.1111/apt.18403 https://doi.org/10.1111/apt.18491. nothing report.

Language: Английский

---

Donafenib combined with sintilimab for advanced hepatocellular carcinoma: a single arm phase II trial

BMC Cancer, Journal Year: 2025, Volume and Issue: 25(1)

Published: Feb. 5, 2025

Language: Английский

---

Advanced lung cancer inflammation index predicts overall survival of hepatocellular carcinoma after hepatectomy

Frontiers in Oncology, Journal Year: 2024, Volume and Issue: 14

Published: Feb. 8, 2024

Aim Limited data are available regarding ALI’s clinical relevance and prognostic value in patients with hepatocellular carcinoma (HCC) after hepatectomy. Materials methods HCC who received hepatectomy at the Meizhou People’s Hospital from May 2011 to February 2022 were enrolled study cohort. The ALI was calculated as follows: = BMI (kg/m 2 ) × ALB (g/dL)/(absolute neutrophil count/absolute lymphocyte count). primary outcome overall survival (OS). secondary cancer-specific (CSS). Univariate multivariate Cox regression analyses performed, followed by nomogram construction decision curve analysis (DCA). Results 425 for analyses. Lower preoperative significantly correlated incomplete tumor capsule advanced stage. an adverse independent factor OS (HR: 1.512, 95% CI: 1.122-2.039, P 0.007) CSS 1.754, 1.262-2.438, &lt;0.001) patients. plot built based on three (including age, TNM stage, ALI) two stage factors CSS, respectively. Further indicated that had better predictive some net benefit than traditional alone, especially long-term OS. Conclusions Our further could be a marker hepatectomy,

Language: Английский

---

Combined hepatocellular-cholangiocarcinoma: from genesis to molecular pathways and therapeutic strategies

Journal of Cancer Research and Clinical Oncology, Journal Year: 2024, Volume and Issue: 150(5)

Published: May 23, 2024

Abstract Hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) are the most common primary liver cancers. Little is known about combined hepatocellular-cholangiocarcinoma (cHCC-ICC) variant proper therapeutic strategies. Out of over 1200 available studies cHCC-ICC, we selected representative ones that reflected updated information with application to individualized therapy. Based on literature data own experience, hypothesize two molecular groups cHCC-ICC can be identified. The proposed division might have a significant role. Most cases develop, like HCC, background cirrhosis hepatitis share characteristics HCC; thus, they named HCC-type strategies those for HCC. This review also highlights new carcinogenic perspective identifies, based second called ICC-type cHCC-ICC. Contrary these show tendency lymph node metastases ICC components in metastatic tissues. No guidelines been established yet such cases. Individualized therapy should be, however, oriented toward immunoprofile tumor cells, different used patients HCC- versus

Language: Английский

---