Single-cell RNA sequencing reveals a reprogramming of hepatic immune cells and a protective role for B cells in MASH-driven HCC

Hepatology Communications, Journal Year: 2025, Volume and Issue: 9(5)

Published: April 21, 2025

Background: HCC, the most common form of liver cancer, is one leading causes cancer-related deaths worldwide. Although immune system plays a crucial role in cancer pathogenesis, landscape within metabolic dysfunction–associated steatohepatitis–driven HCC remains poorly understood. Methods: In this study, we used high-fat, high-carbohydrate diet fed major urinary protein–urokinase-type plasminogen activator mouse model HCC. We performed single-cell RNA sequencing on intrahepatic cells to characterize their heterogeneity and gene expression profiles. Additionally, examined B antitumor immunity by depleting μMT mice analyzing effects progression. Results: Our analysis revealed significant shifts cell populations, including cells, T macrophages that undergo transcriptional reprogramming, suggesting altered roles tumor immunity. Notably, an expanded subset activated showed signature associated with increased survival patients cancer. Consistently, cell-deficient exacerbated progression, substantial reduction lymphocytes, impaired CD8 + activation, may promote enhancing responses. Conclusions: findings reveal complex reprogramming microenvironment underscore protective for These results highlight as potential targets immunomodulatory therapies

Language: Английский

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Identification of B cell antigens in solid cancer: initial insights and functional implications

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: April 28, 2025

Cancer antigen discovery has mostly focused on T cell antigens, while antigens driving B responses have been largely overlooked despite representing another important branch of adaptive immune in cancer. Traditional cancer studied using serological approaches analyzing polyclonal antibodies serum. With recent technological advances single-cell sequencing, a few studies begun to investigate single specificity the tumor microenvironment immunoglobulin recombinant monoclonal antibody production, binding screening, and identification. In this review, we highlight initial insights into directed categorize them cancer-associated viral non-viral with latter featuring autoantigens. We will further discuss functions cells context their specificity, effector function, activation, secretion. Lastly, provide perspectives challenges opportunities identification new translational potential.

Language: Английский

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Induced B cell receptor diversity predicts PD-1 blockade immunotherapy response

Proceedings of the National Academy of Sciences, Journal Year: 2025, Volume and Issue: 122(18)

Published: May 2, 2025

Immune checkpoint inhibitors such as anti-Programmed Death-1 antibodies (aPD-1) can be effective in treating advanced cancers. However, many patients do not respond, and the mechanisms underlying these differences remain incompletely understood. In this study, we profile a cohort of with locally or metastatic basal cell carcinoma undergoing aPD-1 therapy using single-cell RNA sequencing, high-definition spatial transcriptomics tumors draining lymph nodes, immunoreceptor profiling, long-term clinical follow-up. We find that successful responses to PD-1 inhibition are characterized by an induction B receptor (BCR) clonal diversity after treatment initiation. These induced BCR clones spatially colocalize T clones, facilitate their activation, traffic alongside them between tumor nodes enhance clearance. Furthermore, validated aPD-1-induced predictor response larger glioblastoma, melanoma, head neck squamous patients, suggesting is generalizable across types pretreatment harbor characteristic gene expression signature portends higher probability inducing therapy, develop machine learning model predicts PD-1-induced from baseline sequencing. findings underscore dynamic role during immunotherapy, highlighting its importance prognostic marker potential target for intervention non-responders.

Language: Английский

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Potassium ion channel modulation at cancer-neural interface enhances neuronal excitability in epileptogenic glioblastoma multiforme

Neuron, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 1, 2024

Language: Английский

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Induced B-Cell Receptor Diversity Predicts PD-1 Blockade Immunotherapy Response.

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

Published: Dec. 4, 2024

Immune checkpoint inhibitors such as anti-PD-1 antibodies (aPD1) can be effective in treating advanced cancers. However, many patients do not respond and the mechanisms underlying these differences remain incompletely understood. In this study, we profile a cohort of with locally-advanced or metastatic basal cell carcinoma undergoing aPD-1 therapy using single-cell RNA sequencing, high-definition spatial transcriptomics tumors draining lymph nodes, immunoreceptor profiling, long-term clinical follow-up. We find that successful responses to PD-1 inhibition are characterized by an induction B-cell receptor (BCR) clonal diversity after treatment initiation. These induced BCR clones spatially co-localize T-cell clones, facilitate their activation, traffic alongside them between tumor nodes enhance clearance. Furthermore, validated aPD1-induced predictor response larger glioblastoma, melanoma, head neck squamous patients, suggesting is generalizable across types discover pre-treatment harbor characteristic gene expression signature portends higher probability inducing therapy, develop machine learning model predicts PD-1-induced from baseline sequencing. findings underscore dynamic role B during immunotherapy, highlighting its importance prognostic marker potential target for intervention non-responders.

Language: Английский

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