Trial reportGut2025
Multiomics analysis of immune correlatives in hepatocellular carcinoma patients treated with tremelimumab plus durvalumab.
Trial report in Gut, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02821754 (A Pilot Study of Combined Immune Checkpoint Inhibition in Combination With Ablative Therapies in Subjects With Hepatocellular Carcinoma), which is not on this map. Cited by 16 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
A Pilot Study of Combined Immune Checkpoint Inhibition in Combination With Ablative Therapies in Subjects With Hepatocellular Carcinoma (HCC) or Biliary Tract Carcinomas (BTC)
Who cites it
16 citing papers in PubMed.
- Optimal treatment selection for hepatocellular carcinoma in the era of immunotherapy.Journal of gastroenterology · 2026Review
- The effect of prior transarterial chemoembolization on response to immune checkpoint inhibitor treatment in patients with hepatocellular carcinoma.Clinical and molecular hepatology · 2026Article
- Acquired Genetic Variants, Not Tumor Mutation Burden, Drive Resistance to Immunotherapy in Hepatocellular Carcinoma.Liver cancer · 2026Article
- Review
- Systemic immune profiling uncovers divergent mechanisms and predictive biomarkers of response to combination immunotherapies in hepatocellular carcinoma.Journal for immunotherapy of cancer · 2026Article
- IL-1 family of cytokines in gastrointestinal and liver disorders.Nature reviews. Gastroenterology & hepatology · 2026Review
- The Role of Talaromyces Marneffei Binding To CD86 in the CD86-CTLA4 Regulatory Pathway.Current microbiology · 2025Article
- The efficacy of atezolizumab plus bevacizumab for advanced hepatocellular carcinoma in relation to tumor-infiltrating lymphocytes.JHEP reports : innovation in hepatology · 2025Article
- Article
- Inflammation and immunity in liver homeostasis and disease: a nexus of hepatocytes, nonparenchymal cells and immune cells.Cellular & molecular immunology · 2025Review
- Targeting tumor-associated macrophages to overcome immune checkpoint inhibitor resistance in hepatocellular carcinoma.Journal of experimental & clinical cancer research : CR · 2025Review
- Spatial immune scoring and prediction of HCC outcomes.JHEP reports : innovation in hepatology · 2025Article
- Application of single-cell and spatial omics in deciphering cellular hallmarks of cancer drug response and resistance.Journal of hematology & oncology · 2025Review
- SPP1 + macrophages cause exhaustion of tumor-specific T cells in liver metastases.Nature communications · 2025Article
- Adrenomedullin orchestrates treatment resistance in hepatocellular carcinoma via immune microenvironment remodeling.Frontiers in genetics · 2025Article
- Heterogeneity of monocytes in cancer.American journal of cancer research · 2025Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
38 authors.
Funding
Abstract
backgroundHepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality. The combination of tremelimumab and durvalumab is now a standard treatment option for advanced HCC.
objectiveTo study immune responses in HCC patients treated with tremelimumab and durvalumab.
designWe treated 28 HCC patients with durvalumab, tremelimumab and locoregional therapies. We performed a high-dimensional multiomics analysis including whole exome sequencing, single-cell RNA seq, CO-Detection by indEXing, flow cytometry and multiplex cytokine/chemokine analysis of patients' blood and tumour samples and integrated this data to elucidate immune correlatives and response mechanisms. Mice with syngeneic HCC were treated with anti-PD-L1 plus anti-CTLA4 for hepatic lymphocytes, tumour-infiltrating lymphocytes and peripheral blood mononuclear cell analysis.
resultsThe median overall survival was 19.2 months. Tumour tissue analysis revealed enhanced interferon responses, with stronger effects in responders. Gene set variation analysis indicated enhanced antigen presentation in responders. Spatial analysis revealed that non-responder tumours had higher numbers of Tregs located in neighbourhoods enriched with immune cells and expressed higher levels of ICOS and PD-1. Conversely, non-responder PD1+CD8+T in these Treg-enriched neighbourhoods expressed lower ICOS. Cell-communication analysis demonstrated that Treg-CD8+T interaction was enhanced in non-responder tissue. Peripheral blood analysis showed increased classical monocytes in responders and Tregs in non-responders. Treg-CD8+T interaction was confirmed in preclinical models. Finally, single-patient computational analysis from the all-across analysis was performed on 860 features, which led to the identification of multiomics feature sets including Treg features.
conclusionOur study provides a blueprint for in-depth analysis of immune correlates in immunotherapy studies and demonstrates the importance of Treg distribution in HCC. TRIAL REGISTRATION NUMBERS: NCT02821754 and the EudraCT identifier: 2019-002767-98.
Indexed as
Identifiers
What Socratic holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.