Combined analysis of bulk and single-cell RNA sequencing reveals novel natural killer cell-related prognostic biomarkers for predicting immunotherapeutic response in hepatocellular carcinoma DOI Creative Commons
Kai Zhang, Enwu Yuan

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: March 28, 2023

Introduction Natural killer (NK) cells play an irreplaceable and important role as a subtype of innate immune in the contemporary setting antitumor immunity. Methods We chose total 1,196 samples for this analysis from public dataset’s six separate cohorts. To identify 42 NK cell marker genes, we first carried out thorough study single-cell RNA sequencing data GSE149614 cohort hepatocellular carcinoma (HCC). Results Using genes TCGA cohort, next created seven-gene prognostic signature, separating patients into two categories with distinct survival patterns. This signature’s prediction ability was well verified across several validation Patients high scores had higher TIDE but lower infiltration percentages. Importantly, low-scoring superior immunotherapy response prognosis than high-scoring independent (IMvigor210). Finally, used CD56 TUBA1B antibodies immunohistochemical labeling HCC tissue sections, discovered number CD56+ sections expression. Discussion In summary, our research unique profile based on that may accurately predict how would work patients.

Language: Английский

PANoptosis: bridging apoptosis, pyroptosis, and necroptosis in cancer progression and treatment DOI Creative Commons
Jie Gao,

Anying Xiong,

Jiliu Liu

et al.

Cancer Gene Therapy, Journal Year: 2024, Volume and Issue: 31(7), P. 970 - 983

Published: March 29, 2024

Abstract This comprehensive review explores the intricate mechanisms of PANoptosis and its implications in cancer. PANoptosis, a convergence apoptosis, pyroptosis, necroptosis, plays crucial role cell death immune response regulation. The study delves into molecular pathways each mechanism their crosstalk within emphasizing shared components like caspases PANoptosome complex. It highlights significant various cancers, including respiratory, digestive, genitourinary, gliomas, breast showing impact on tumorigenesis patient survival rates. We further discuss interwoven relationship between tumor microenvironment (TME), illustrating how influences behavior progression. underscores dynamic interplay tumors microenvironments, focusing roles different cells interactions with cancer cells. Moreover, presents new breakthroughs therapy, potential targeting to enhance anti-tumor immunity. outlines strategies manipulate for therapeutic purposes, such as key signaling molecules caspases, NLRP3, RIPK1, RIPK3. novel treatments immunogenic PANoptosis-initiated therapies nanoparticle-based is also explored.

Language: Английский

Citations

33
Development of a deep pathomics score for predicting hepatocellular carcinoma recurrence after liver transplantation DOI Creative Commons

Wei‐Feng Qu,

Meng‐Xin Tian, Hongwei Lü

et al.

Hepatology International, Journal Year: 2023, Volume and Issue: 17(4), P. 927 - 941

Published: April 8, 2023

Tumor recurrence after liver transplantation (LT) impedes the curative chance for hepatocellular carcinoma (HCC) patients. This study aimed to develop a deep pathomics score (DPS) predicting tumor using learning.Two datasets of 380 HCC patients who underwent LT were enrolled. Residual convolutional neural networks used identify six histological structures HCC. The individual risk each structure and DPS derived by modified DeepSurv network. Cox regression analysis Concordance index evaluate prognostic significance. cellular exploration immune biomarkers was performed quantitative spatial proximity according three panels 7-color immunofluorescence.The overall classification accuracy tissue 97%. At structural level, cells most significant category post-LT (HR 1.907, 95% CI 1.490-2.440). C-indices achieved 0.827 0.794 in training validation cohorts, respectively. Multivariate recurrence-free survival (RFS) showed that 4.795, 3.017-7.619) an independent factor. Patients high-risk subgroup had shorter RFS, larger diameter lower proportion clear borders. higher infiltration intratumoral NK negatively correlated with risk.This established effective DPS. Immune related recurrence. well prediction identification clinicopathological features.

Language: Английский

Citations

30
Regulatory T cells and immune escape in HCC: understanding the tumor microenvironment and advancing CAR-T cell therapy DOI Creative Commons

Guangtan Du,

Cunmiao Dou,

Peng Sun

et al.

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: July 29, 2024

Liver cancer, which most commonly manifests as hepatocellular carcinoma (HCC), is the sixth common cancer in world. In HCC, immune system plays a crucial role growth and proliferation of tumor cells. HCC achieve escape through microenvironment, significantly promotes development this cancer. Here, article introduces summarizes functions effects regulatory T cells (Tregs) highlighting how Tregs inhibit regulate cells, cytokines, ligands receptors, etc, thereby promoting escape. addition, it discusses mechanism CAR-T therapy for elaborate on relationship between Tregs.

Language: Английский

Citations

9
Immune checkpoint inhibitors in the treatment of hepatocellular carcinoma DOI Creative Commons
Zeynep Akbulut, Başak Aru, Furkan Aydın

et al.

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: April 4, 2024

Despite advances in cancer treatment, hepatocellular carcinoma (HCC), the most common form of liver cancer, remains a major public health problem worldwide. The immune microenvironment plays critical role regulating tumor progression and resistance to therapy, HCC, (TME) is characterized by an abundance immunosuppressive cells signals that facilitate evasion metastasis. Recently, anti-cancer immunotherapies, therapeutic interventions designed modulate system recognize eliminate have become important cornerstone therapy. Immunotherapy has demonstrated ability improve survival provide durable control certain groups HCC patients, while reducing adverse side effects. These findings represent significant step toward improving treatment outcomes. As clinical trials, administration checkpoint inhibitors (ICIs), particularly combination with anti-angiogenic agents tyrosine kinase inhibitors, prolonged subset patients providing alternative for who progress on first-line In this review, we aimed overview its development, summarize trials involving ICIs, either as monotherapies or other disease. Challenges considerations regarding ICIs are also outlined.

Language: Английский

Citations

8
Immune Checkpoints and the Immunology of Liver Fibrosis DOI Creative Commons
Ioannis Tsomidis, Argyro Voumvouraki, Elias Kouroumalis

et al.

Livers, Journal Year: 2025, Volume and Issue: 5(1), P. 5 - 5

Published: Jan. 27, 2025

Liver fibrosis is a very complicated dynamic process where several immune cells are involved. Both innate and adaptive immunity implicated, their interplay always present. Multi-directional interactions between liver macrophages, hepatic stellate (HSCs), cells, cytokines important for the induction perpetuation of fibrosis. Detailed studies proteomics transcriptomics have produced new evidence role individual in cirrhosis. Most these controlled by various checkpoints whose main function to maintain homeostasis implicated cells. Recent indicates that involved In particular, programmed cell death protein 1 (PD-1), death-ligand (PD-L1), cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) been investigated, particularly after availability checkpoint inhibitors. Their activation leads exhaustion CD4+ve CD8+ve promotion this review, current pathogenesis immunological abnormalities discussed. The recent data on involvement identified as possible targets future interventions.

Language: Английский

Citations

1
The Malignant Transformation of Viral Hepatitis to Hepatocellular Carcinoma: Mechanisms and Interventions DOI Creative Commons
Huimin Yuan, Ruochen Xu, Senlin Li

et al.

MedComm, Journal Year: 2025, Volume and Issue: 6(3)

Published: March 1, 2025

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality globally, predominantly associated with chronic hepatitis B virus (HBV) and C (HCV) infections. These infections drive persistent liver inflammation, culminating in cellular dysregulation, fibrosis, cancer. Despite advancements targeted therapies, drug resistance the lack reliable biomarkers for patient stratification still terribly hinder treatment viral HCC. To this end, review delves into intricate mechanisms underlying malignant transformation to HCC, including integration, genomic instability, epigenetic modifications, oxidative stress, gut microbiota dysbiosis, immune escape, abnormal signaling pathways, highlighting their complex interactions synergies. Cutting-edge preclinical clinical HCC management, lifestyle immunotherapies, gene-based approaches, innovative treatments, are further investigated, particular priority given therapeutic potential future applications overcoming current limitations. By synthesizing recent scientific insights, aims deepen understanding pathogenesis context hepatitis, paving way novel targets personalized strategies, ultimately improving outcomes.

Language: Английский

Citations

1
Macrophage metabolism, phenotype, function, and therapy in hepatocellular carcinoma (HCC) DOI Creative Commons

Jingquan Huang,

Qiulin Wu,

David A. Geller

et al.

Journal of Translational Medicine, Journal Year: 2023, Volume and Issue: 21(1)

Published: Nov. 15, 2023

Abstract The pivotal role of the tumor microenvironment (TME) in initiation and advancement hepatocellular carcinoma (HCC) is widely acknowledged, as it fosters proliferation metastasis HCC cells. Within intricate TME HCC, tumor-associated macrophages (TAMs) represent a significant constituent non-malignant TAMs engage direct communication with cancer cells while also exerting influence on other immune to adopt tumor-supportive phenotype that facilitates progression. Among multifaceted mechanisms at play, metabolic reprogramming both leads phenotypic alterations functional modifications macrophages. This comprehensive review elucidates interplay between cellular metabolism macrophage phenotype/polarization, providing an overview associated signaling molecules potential therapeutic strategies for HCC.

Language: Английский

Citations

22
Construction of the panoptosis-related gene model and characterization of tumor microenvironment infiltration in hepatocellular carcinoma DOI Creative Commons
Xinrui Shi, Xia Gao,

W. Liu

et al.

Oncology Research Featuring Preclinical and Clinical Cancer Therapeutics, Journal Year: 2023, Volume and Issue: 31(4), P. 569 - 590

Published: Jan. 1, 2023

Hepatocellular carcinoma (HCC) is the most common fatal cancer worldwide, patients with HCC have a high mortality rate and poor prognosis.PANoptosis novel discovery of programmed cell death associated development.However, role PANoptosis in remains obscure.In this study, we enrolled 274 PANoptosisrelated genes (PANRGs) screened 8 to set up prognostic model.A previous scoring system calculated PANscore was utilized quantify individual risk level each patient, reliability model has been validated an external cohort.Nomogram constructed clinical characteristics were used optimize individualized treatment for patient.Single-cell analysis revealed tumor immune infiltration, particularly natural killer (NK) cells.Further exploration hub assessment these 4 by quantitative real-time PCR (qRT-PCR) immunohistochemistry (IHC).In conclusion, evaluated PANoptosis-based as potential biomarker patients.

Language: Английский

Citations

17
Application of adoptive cell therapy in hepatocellular carcinoma DOI Open Access

Dengqiang Wu,

Yujie Li

Immunology, Journal Year: 2023, Volume and Issue: 170(4), P. 453 - 469

Published: July 12, 2023

Abstract Hepatocellular carcinoma (HCC) remains a global health challenge. Novel treatment modalities are urgently needed to extend the overall survival of patients. The liver plays an immunomodulatory function due its unique physiological structural characteristics. Therefore, following surgical resection and radiotherapy, immunotherapy regimens have shown great potential in hepatocellular carcinoma. Adoptive cell is rapidly developing In this review, we summarize latest research on adoptive for focus chimeric antigen receptor (CAR)‐T cells T (TCR) engineered cells. Then tumour‐infiltrating lymphocytes (TILs), natural killer (NK) cells, cytokine‐induced (CIK) macrophages briefly discussed. main overview application challenges It aims provide reader with comprehensive understanding current status HCC offers some strategies. We hope new ideas clinical

Language: Английский

Citations

16
Key oncogenic signaling pathways affecting tumor-infiltrating lymphocytes infiltration in hepatocellular carcinoma: basic principles and recent advances DOI Creative Commons
Xiang Wang, Zijun Yuan, Zhengbo Li

et al.

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: Feb. 15, 2024

The incidence of hepatocellular carcinoma (HCC) ranks first among primary liver cancers, and its mortality rate exhibits a consistent annual increase. treatment HCC has witnessed significant surge in recent years, with the emergence targeted immune therapy as an adjunct to early surgical resection. Adoptive cell (ACT) using tumor-infiltrating lymphocytes (TIL) shown promising results other types solid tumors. This article aims provide comprehensive overview intricate interactions between different TILs their impact on HCC, elucidate strategies for targeting neoantigens through TILs, address challenges encountered TIL therapies along potential solutions. Furthermore, this specifically examines oncogenic signaling pathways activation within tumor microenvironment infiltration dynamics TILs. Additionally, concise is provided regarding preparation techniques update clinical trials investigating TIL-based immunotherapy

Language: Английский

Citations

5