Sex disparities matter in cancer development and therapy

Nature reviews. Cancer, Journal Year: 2021, Volume and Issue: 21(6), P. 393 - 407

Published: April 20, 2021

Language: Английский

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T-Cell Hyperactivation and Paralysis in Severe COVID-19 Infection Revealed by Single-Cell Analysis

Frontiers in Immunology, Journal Year: 2020, Volume and Issue: 11

Published: Oct. 8, 2020

Severe COVID-19 patients show various immunological abnormalities including T-cell reduction and cytokine release syndrome, which can be fatal is a major concern of the pandemic. However, it poorly understood how dysregulation contribute to pathogenesis severe COVID-19. Here we single cell-level mechanisms for in COVID-19, demonstrating new pathogenetic activation differentiation underlying By silico sorting CD4+ T-cells from cell RNA-seq dataset, found that were highly activated showed unique pathways lung patients. Notably, those expressed immunoregulatory receptors CD25, whilst repressing expression FOXP3. Furthermore, CD25+ hyperactivated differentiate into multiple helper lineages, showing multifaceted effector with Th1 Th2 characteristics. Lastly, CD25- expressing produce protease Furin, facilitates viral entry SARS-CoV-2. Collectively, are FOXP3-mediated negative feedback impaired lung, may promote immunopathology. Therefore, our study proposes model hyperactivation paralysis drives immunopathology

Language: Английский

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Regulatory T Cells: Regulation of Identity and Function

Frontiers in Immunology, Journal Year: 2021, Volume and Issue: 12

Published: Oct. 5, 2021

T regulatory cells suppress a variety of immune responses to self-antigens and play role in peripheral tolerance maintenance by limiting autoimmune disorders, other pathological such as reactivity oncoprotein encoded antigens. Forkhead box P3 (FOXP3) expression is required for Treg stability affects functional activity. Mutations the master regulator FOXP3 related components have been linked diseases humans, IPEX, scurfy-like phenotype mice. Several lines evidence indicate that use immunosuppressive mechanisms limit an response targeting effector cells, including secretion immunoregulatory cytokines, granzyme/perforin-mediated cell cytolysis, metabolic perturbation, directing maturation function antigen-presenting (APC) extracellular vesicles development immunological tolerance. In this review, several highlighted discussed.

Language: Английский

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Potential anti-tumor effects of regulatory T cells in the tumor microenvironment: a review

Journal of Translational Medicine, Journal Year: 2024, Volume and Issue: 22(1)

Published: March 20, 2024

Abstract Regulatory T cells (Tregs) expressing the transcription factor FoxP3 are essential for maintaining immunological balance and a significant component of immunosuppressive tumor microenvironment (TME). Single-cell RNA sequencing (ScRNA-seq) technology has shown that Tregs exhibit plasticity functional diversity in various tumors within TME. This results playing dual role TME, which is not always centered around supporting progression as typically believed. Abundant data confirms anti-tumor activities their correlation with enhanced patient prognosis specific types malignancies. In this review, we summarize potential actions Tregs, including suppressing tumor-promoting inflammatory responses boosting immunity. addition, study outlines spatial temporal variations function to emphasize predictive significance malignancies may change. It comprehend effects improve therapy strategies.

Language: Английский

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Targeting the NF-κB pathway as a potential regulator of immune checkpoints in cancer immunotherapy

Cellular and Molecular Life Sciences, Journal Year: 2024, Volume and Issue: 81(1)

Published: Feb. 29, 2024

Abstract Advances in cancer immunotherapy over the last decade have led to development of several agents that affect immune checkpoints. Inhibitory receptors expressed on T cells negatively regulate response include cytotoxic T‑lymphocyte antigen 4 (CTLA4) and programmed cell death protein 1 (PD1), which been studied more than similar receptors. Inhibition these proteins other checkpoints can stimulate system attack cells, prevent tumor from escaping response. However, administration anti-PD1 anti-CTLA4 antibodies has associated with adverse inflammatory responses autoimmune diseases. The current review discussed role NF-κB pathway as a promoter, how it govern various More precise knowledge about communication between pathways could increase effectiveness reduce effects checkpoint inhibitor therapy. Graphical abstract

Language: Английский

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The Spectrum ofHelicobacter-Mediated Diseases

Annual Review of Pathology Mechanisms of Disease, Journal Year: 2020, Volume and Issue: 16(1), P. 123 - 144

Published: Nov. 16, 2020

Helicobacter pylori is the leading cause of peptic ulcer disease. The infection has been implicated in more than 75% duodenal cases and 17% gastric cases. H. classified as a human carcinogen, since it main distal adenocarcinoma B cell mucosa-associated lymphoid tissue lymphoma. Evidence also links with extragastric conditions including iron deficiency anemia, idiopathic thrombocytopenic purpura, vitamin B12 deficiency. Studies indicate that may be protective against other gastrointestinal tract (e.g., reflux esophagitis related pathologies) elsewhere body asthma). asymptomatic vast majority cases; serious outcomes occur only 10-15% infected individuals. Despite extensive research over past 3 decades, there no effective vaccine, circumstances to disease development remain unclear. In addition, now growing prevalence antimicrobial resistance pylori. This review discusses these important issues.

Language: Английский

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Thymus and autoimmunity

Seminars in Immunopathology, Journal Year: 2021, Volume and Issue: 43(1), P. 45 - 64

Published: Feb. 1, 2021

Abstract The thymus prevents autoimmune diseases through mechanisms that operate in the cortex and medulla, comprising positive negative selection generation of regulatory T-cells (Tregs). Egress from perivascular space (PVS) to blood is another possible checkpoint, as shown by some autoimmune/immunodeficiency syndromes. In polygenic diseases, subtle thymic dysfunctions may compound genetic, hormonal environmental cues. Here, we cover (a) tolerance-inducing cell types, whether epithelial or tuft cells, dendritic, B- myoid cells; (b) their failure relation anatomic compartments, with special emphasis on human monogenic related pathologies, if known; (c) polymorphisms mutations tolerance-related genes an impact (e.g. gene encoding thymoproteasome-specific subunit, PSMB11 ), promiscuous expression AIRE , PRKDC FEZF2 CHD4 Treg development SATB1 FOXP3 T-cell migration TAGAP ) egress MTS1 CORO1A ); (d) myasthenia gravis prototypic outcome inflamed disordered neoplastic ‘sick thymus’.

Language: Английский

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Radiotherapy remodels the tumor microenvironment for enhancing immunotherapeutic sensitivity

Cell Death and Disease, Journal Year: 2023, Volume and Issue: 14(10)

Published: Oct. 13, 2023

Cancer immunotherapy has transformed traditional treatments, with immune checkpoint blockade being particularly prominent. However, minimal benefit for patients in most types of cancer and is largely ineffective some cancers (such as pancreatic glioma). A synergistic anti-tumor response may be produced through the combined application tumor treatment methods. Radiotherapy (RT) not only kills cells but also triggers pro-inflammatory molecules' release cell infiltration, which remodel microenvironment (TME). Therefore, combination RT expected to achieve improved efficacy. In this review, we summarize effects on cellular components TME, including T receptor repertoires, different subsets, metabolism, tumor-associated macrophages other myeloid (dendritic cells, myeloid-derived suppressor neutrophils eosinophils). Meanwhile, non-cellular such lactate extracellular vesicles are elaborated. addition, discuss impact modalities immunity issues related clinical practice therapy.

Language: Английский

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Epigenetic regulation and T-cell responses in endometriosis – something other than autoimmunity

Frontiers in Immunology, Journal Year: 2022, Volume and Issue: 13

Published: July 22, 2022

Endometriosis is defined as the presence of endometrial-like glands and stroma located outside uterine cavity. This common, estrogen dependent, inflammatory condition affects up to 15% reproductive-aged women a well-recognized cause chronic pelvic pain infertility. Despite still unknown etiology endometriosis, much evidence suggests participation epigenetic mechanisms in disease etiopathogenesis. The main rationale based on fact that heritable phenotype changes do not involve alterations DNA sequence are common triggers for hormonal, immunological, disorders, which play key role formation endometriotic foci. Epigenetic regulating T-cell responses, including methylation posttranslational histone modifications, deserve attention because tissue-resident T lymphocytes work concert with organ structural cells generate appropriate immune responses functionally shaped by organ-specific environmental conditions. Thus, failure precisely regulate cell transcription may result compromised immunological integrity an increased risk disorders. coexistence endometriosis autoimmunity well-known occurrence. Recent research results indicate regulatory (Treg) number highly active Tregs macrophages have been found peritoneal fluid from endometriosis. Elimination function imbalance between helper Th1 Th2 types reported endometria endometriosis-associated review aims present state art recognition reprogramming factor pathophysiology context T-cell-related autoimmunity. new potential therapeutic approaches modulation and/or adoptive transfer will also be outlined.

Language: Английский

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YTHDF2/m⁶A/NF‐κB axis controls anti‐tumor immunity by regulating intratumoral Tregs

The EMBO Journal, Journal Year: 2023, Volume and Issue: 42(15)

Published: June 22, 2023

Language: Английский

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