A single-cell atlas of the multicellular ecosystem of primary and metastatic hepatocellular carcinoma

Nature Communications, Год журнала: 2022, Номер 13(1)

Опубликована: Авг. 6, 2022

Abstract Hepatocellular carcinoma (HCC) represents a paradigm of the relation between tumor microenvironment (TME) and development. Here, we generate single-cell atlas multicellular ecosystem HCC from four tissue sites. We show enrichment central memory T cells (T CM ) in early tertiary lymphoid structures (E-TLSs) assess relationships chronic HBV/HCV infection cell infiltration exhaustion. find MMP9 + macrophages to be terminally differentiated tumor-associated (TAMs) PPARγ pivotal transcription factor driving their differentiation. also characterize heterogeneous subpopulations malignant hepatocytes multifaceted functions shaping immune HCC. Finally, identify seven microenvironment-based subtypes that can predict prognosis patients. Collectively, this large-scale deepens our understanding microenvironment, which might facilitate development new therapy strategies for malignancy.

Язык: Английский

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Single-cell atlas of healthy human blood unveils age-related loss of NKG2C+GZMB−CD8+ memory T cells and accumulation of type 2 memory T cells

Immunity, Год журнала: 2023, Номер 56(12), С. 2836 - 2854.e9

Опубликована: Ноя. 13, 2023

Extensive, large-scale single-cell profiling of healthy human blood at different ages is one the critical pending tasks required to establish a framework for systematic understanding aging. Here, using RNA/T cell receptor (TCR)/BCR-seq with protein feature barcoding, we profiled 317 samples from 166 individuals aged 25-85 years old. From this, generated dataset ∼2 million cells that described 55 subpopulations immune cells. Twelve changed age, including accumulation GZMK

Язык: Английский

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The interaction of innate immune and adaptive immune system

MedComm, Год журнала: 2024, Номер 5(10)

Опубликована: Сен. 15, 2024

The innate immune system serves as the body's first line of defense, utilizing pattern recognition receptors like Toll-like to detect pathogens and initiate rapid response mechanisms. Following this initial response, adaptive immunity provides highly specific sustained killing via B cells, T antibodies. Traditionally, it has been assumed that activates immunity; however, recent studies have revealed more complex interactions. This review a detailed dissection composition function systems, emphasizing their synergistic roles in physiological pathological contexts, providing new insights into link between these two forms immunity. Precise regulation both systems at same time is beneficial fight against immune-related diseases, for example, cGAS-STING pathway found play an important role infections cancers. In addition, paper summarizes challenges future directions field immunity, including latest single-cell sequencing technologies, CAR-T cell therapy, checkpoint inhibitors. By summarizing developments, aims enhance our understanding complexity interactions perspectives system.

Язык: Английский

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MAIT cells confer resistance to Lenvatinib plus anti-PD1 antibodies in hepatocellular carcinoma through TNF-TNFRSF1B pathway

Clinical Immunology, Год журнала: 2023, Номер 256, С. 109770 - 109770

Опубликована: Сен. 17, 2023

Язык: Английский

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Different subpopulations of regulatory T cells in human autoimmune disease, transplantation, and tumor immunity

MedComm, Год журнала: 2022, Номер 3(2)

Опубликована: Апрель 21, 2022

Abstract CD4 + CD25 regulatory T cells (Tregs), a subpopulation of naturally that characteristically express transcription factor Forkhead box P3 (FOXP3), play pivotal role in the maintenance immune homeostasis and prevention autoimmunity. With development biological technology, understanding plasticity stability Tregs has been further developed. Recent studies have suggested human are functionally phenotypically diverse. The functions mechanisms different phenotypes disease settings, such as tumor microenvironment, autoimmune diseases, transplantation, gradually become hot spots immunology research arouse extensive attention. Among complex functions, FOXP3 possess potent immunosuppressive capacity can produce various cytokines, IL‐2, IL‐10, TGF‐β, to regulate homeostasis. They alleviate progression diseases by resisting inflammatory responses, whereas promoting poor prognosis helping evade surveillance or suppressing effector activity. Therefore, methods for targeting their depleting them strengthen immunity expanding treat immunological need be Here, we discuss subpopulations essential immunotherapeutic strategies involving diseases.

Язык: Английский

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Regulatory T-cells: The Face-off of the Immune Balance

Frontiers in Bioscience-Landmark, Год журнала: 2024, Номер 29(11)

Опубликована: Ноя. 8, 2024

Regulatory T-cells (Tregs) play a crucial role in maintaining immune homeostasis, ensuring balanced response. Tregs primarily operate an antigen-specific fashion, facilitated by their distinct distribution within discrete niches. have been studied extensively, from point of origin the thymus to fate periphery or organs. Signals received antigen-presenting cells (APCs) stimulate dampen inflammation. Almost all tumors are characterized pathological abundance suppression microenvironment. Conversely, lack thereof proves detrimental immunological disorders. Achieving expression relation other compartments is important establishing effective and adaptable tolerance towards cancer autoantigens. In context cancer, it essential decrease frequency overcome tumor suppression. A lower survival rate associated with presence excessive exhausted effector increased regulatory cells. However, when comes treating graft rejection autoimmune diseases, focus lies on transfer Tregs. Here, we explore complex mechanisms that use human disease balance

Язык: Английский

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Conversion of T Effector Cells Into T Regulatory Cells in Type 1 Diabetes/Latent Autoimmune Diabetes of Adults by Inhibiting eIF5A and Notch Pathways

ImmunoTargets and Therapy, Год журнала: 2025, Номер Volume 14, С. 205 - 226

Опубликована: Март 1, 2025

The generation of functionally active, stable T regulatory cells (Tregs) is a crucial target type 1 diabetes (T1D) immunotherapy. This study investigated therapeutic intervention for T1D/Latent autoimmune in adults (LADA), wherein the diabetogenic proinflammatory Treg (intermediate) cell subset was characterized and driven to phenotype (CD4+CD25+FOXP3+). involved simultaneous inhibition eukaryotic initiation factor 5a (eIF5a) Notch pathways using GC7 (N1-Guanyl-1,7-diaminoheptane) Anti-DLL4 (Delta-like-ligand-4). Peripheral blood from patients with T1D/LADA healthy (n=7 each) used isolate CD4+CD25- population CD4 deficient peripheral mononuclear (PBMCs). Cells were subjected GAD65+GC7+anti-DLL4 treatment seven days compared conventional anti-CD3/CD28/CD137 stimulation conversion into Tregs. Newly plasticized Tregs assessed their suppressive potential against freshly isolated autologous responder cells. In addition, live, dead, apoptotic counts performed evaluate adverse effects immunomodulatory on immune data analyzed GraphPad Prism 1- or 2-way ANOVA Student's t-test. A unique cytokines expressing intermediate (CD4+CD25-IFNg+IL17+FOXP3+) found significantly increased age-matched adults. Simultaneous eIF5a could induce Treg-deficient CD4+ PBMCs patients. withstanding milieu mimicking T1D/LADA, exhibited functional phenotype. Furthermore, had no cells.The present approach multipronged involving that addresses upregulation tolerance, differentiation, proliferation cytotoxic alleviates β-cell dysfunction. Additionally, this strategy also be leveraged boost following islet transplantation as combinational therapy along adoptive transfer.

Язык: Английский

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The influence of fatty acid metabolism on T cell function in lung cancer

FEBS Journal, Год журнала: 2025, Номер unknown

Опубликована: Март 25, 2025

The tumor microenvironment (TME) is a complex ecosystem, encompassing variety of cellular and non-cellular elements surrounding interacting with cancer cells, overall promoting growth, immune evasion, therapy resistance. In the context solid tumors, factors, such as hypoxia, nutritional competition, increased stress responses, glucose demand, PD-1 signals strongly influence metabolic alterations in TME, highly contributing to maintenance tumor-supportive immune-suppressive milieu. Cancer cell-induced partly result an fatty acid (FA) metabolism within which favors recruitment M2 macrophages myeloid-derived suppressor crucial contributors T-cell exhaustion, exclusion, decreased effector functions. drastic pro-tumoral changes induced by rewiring signaling loops that support progression metastatic spreading, negatively impact efficacy. As tumor- are increasingly gaining attention due their potential therapeutic implications, we discuss effects altered lipid on progression, response, efficacy lung cancer. particular, focus our analysis tumor-induced experienced T lymphocytes possible strategies overcome immunotherapy resistance targeting specific pathways cells.

Язык: Английский

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Many Faces of Regulatory T Cells: Heterogeneity or Plasticity?

Cells, Год журнала: 2024, Номер 13(11), С. 959 - 959

Опубликована: Июнь 1, 2024

Regulatory T cells (Tregs) are essential for maintaining the immune balance in normal and pathological conditions. In autoimmune diseases transplantation, they restrain loss of self-tolerance promote engraftment, whereas cancer, an increase Treg numbers is mostly associated with tumor growth poor prognosis. Numerous markers their combinations have been used to identify subsets, demonstrating phenotypic diversity Tregs. The complexity identification can be hampered by unstable expression some markers, decrease a specific marker over time or emergence new marker. It remains unclear whether such shifts due conditions observed changes initially different populations. first case, cellular plasticity observed, second, heterogeneity observed. difference between these terms relation Tregs rather blurred. Considering promising perspectives regenerative cell-based therapy, existing confusing data on phenotypes require further investigation analysis. our review, we introduce criteria that allow us distinguish normally pathologically, taking closer look at drawing line two terms.

Язык: Английский

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Biomarkers and experimental models for cancer immunology investigation

MedComm, Год журнала: 2023, Номер 4(6)

Опубликована: Дек. 1, 2023

Abstract The rapid advancement of tumor immunotherapies poses challenges for the tools used in cancer immunology research, highlighting need highly effective biomarkers and reproducible experimental models. Current immunotherapy encompass surface protein markers such as PD‐L1, genetic features microsatellite instability, tumor‐infiltrating lymphocytes, liquid biopsy circulating DNAs. Experimental models, ranging from 3D vitro cultures (spheroids, submerged air–liquid interface organ‐on‐a‐chips) to advanced bioprinting techniques, have emerged valuable platforms investigations biomarker research. By preserving native immune components or coculturing with exogenous cells, these models replicate microenvironment vitro. Animal like syngeneic genetically engineered patient‐derived xenografts provide opportunities study vivo tumor‐immune interactions. Humanized animal further enable simulation human‐specific microenvironment. Here, we a comprehensive overview advantages, limitations, prospects different specifically focusing on role predicting outcomes ability integrating cutting‐edge this review serves resource accessing forefront investigation.

Язык: Английский

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