Targeting JMJD1C to selectively disrupt tumor Treg cell fitness enhances antitumor immunity

Nature Immunology, Journal Year: 2024, Volume and Issue: 25(3), P. 525 - 536

Published: Feb. 14, 2024

Language: Английский

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Converting “cold” to “hot”: epigenetics strategies to improve immune therapy effect by regulating tumor‐associated immune suppressive cells

Cancer Communications, Journal Year: 2024, Volume and Issue: 44(6), P. 601 - 636

Published: May 7, 2024

Abstract Significant developments in cancer treatment have been made since the advent of immune therapies. However, there are still some patients with malignant tumors who do not benefit from immunotherapy. Tumors without immunogenicity called “cold” which unresponsive to immunotherapy, and opposite “hot” tumors. Immune suppressive cells (ISCs) refer can inhibit response such as tumor‐associated macrophages (TAMs), myeloid‐derived suppressor (MDSCs), regulatory T (Treg) so on. The more ISCs infiltrated, weaker tumor, showing characteristics tumor. dysfunction tumor microenvironment (TME) may play essential roles insensitive therapeutic reaction. Previous studies found that epigenetic mechanisms an important role regulation ISCs. Regulating be a new approach transforming into Here, we focused on function TME discussed how epigenetics is involved regulating In addition, summarized by drugs convert immunotherapy‐insensitive immunotherapy‐sensitive would innovative tendency for future immunotherapy

Language: Английский

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Antigen-presenting cells as specialized drivers of intestinal T cell functions

Immunity, Journal Year: 2024, Volume and Issue: 57(10), P. 2269 - 2279

Published: Oct. 1, 2024

Language: Английский

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Stability and plasticity of regulatory T cells in health and disease

Journal of Leukocyte Biology, Journal Year: 2024, Volume and Issue: 116(1), P. 33 - 53

Published: March 1, 2024

The mechanisms that negatively regulate inflammation upon a pathogenic stimulus are crucial for the maintenance of tissue integrity and organ function. T regulatory cells one main drivers in controlling inflammation. ability to adapt different inflammatory cues suppress is relevant features cells. During this process, express transcription factors associated with their counterparts, Th helper cells, including Tbx21, GATA-3, Bcl6, Rorc. acquisition factor helps migrate inflamed tissues. Additionally, have preserve stability while acquiring particular cell subtype. This review focuses on describing subtypes maintain identity health diseases.

Language: Английский

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Current trends in sensitizing immune checkpoint inhibitors for cancer treatment

Molecular Cancer, Journal Year: 2024, Volume and Issue: 23(1)

Published: Dec. 26, 2024

Immune checkpoint inhibitors (ICIs) have dramatically transformed the treatment landscape for various malignancies, achieving notable clinical outcomes across a wide range of indications. Despite these advances, resistance to immune blockade (ICB) remains critical challenge, characterized by variable response rates and non-durable benefits. However, growing research into complex intrinsic extrinsic characteristics tumors has advanced our understanding mechanisms behind ICI resistance, potentially improving outcomes. Additionally, robust predictive biomarkers are crucial optimizing patient selection maximizing efficacy ICBs. Recent studies emphasized that multiple rational combination strategies can overcome enhance susceptibility ICIs. These findings not only deepen tumor biology but also reveal unique action sensitizing agents, extending benefits in cancer immunotherapy. In this review, we will explore underlying ICIs, discuss significance microenvironment (TIME) biomarkers, analyze current outline alternative effectiveness including personalized

Language: Английский

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Expansion of tumor-reactive CD8 ⁺ T cell clonotypes occurs in the spleen in response to immune checkpoint blockade

Science Immunology, Journal Year: 2024, Volume and Issue: 9(99)

Published: Sept. 13, 2024

Immune checkpoint blockade (ICB) enhances T cell responses against cancer, leading to long-term survival in a fraction of patients. CD8 + differentiation response chronic antigen stimulation is highly complex, and it remains unclear precisely which states at anatomic sites are critical for the ICB. We identified an intermediate-exhausted population white pulp spleen that underwent substantial expansion ICB gave rise tumor-infiltrating clonotypes. Increased systemic redirected this toward more circulatory exhausted KLR state, whereas lack cross-presented tumor reduced its spleen. An analogous cells human blood samples exhibited diminished tumor-trafficking ability. Collectively, our data demonstrate role density within clonotypes

Language: Английский

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Architects of immunity: How dendritic cells shape CD8 ⁺ T cell fate in cancer

Science Immunology, Journal Year: 2025, Volume and Issue: 10(103)

Published: Jan. 17, 2025

Immune responses against cancer are dominated by T cell exhaustion and dysfunction. Recent advances have underscored the critical role of early priming interactions in establishing fates. In this review, we explore importance dendritic (DC) signals specifying CD8+ fates cancer, drawing on insights from acute chronic viral infection models. We highlight DCs lymph nodes tumors maintaining stem-like cells, which for durable antitumor immune responses. Understanding how determined will enable rational design immunotherapies, particularly therapeutic vaccines, that can modulate DC-T to generate beneficial

Language: Английский

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STING in Cancer Immunoediting: Modeling Tumor-Immune Dynamics Throughout Cancer Development

Cancer Letters, Journal Year: 2025, Volume and Issue: 612, P. 217410 - 217410

Published: Jan. 16, 2025

Language: Английский

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Immunometabolism of Tregs: mechanisms, adaptability, and therapeutic implications in diseases

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

Published: Jan. 23, 2025

Immunometabolism is an emerging field that explores the intricate interplay between immune cells and metabolism. Regulatory T (Tregs), which maintain homeostasis in immunometabolism, play crucial regulatory roles. The activation, differentiation, function of Tregs are influenced by various metabolic pathways, such as Mammalian targets rapamycin (mTOR) pathway glycolysis. Correspondingly, activated can reciprocally impact these pathways. also possess robust adaptive capabilities, thus enabling them to adapt microenvironments, including tumor microenvironment (TME). complex mechanisms diseases intriguing, particularly conditions like MASLD, where significantly upregulated contribute fibrosis, while diabetes, systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), they show downregulation reduced anti-inflammatory capacity. These phenomena suggest differentiation environment, imbalances either lead development diseases. Thus, moderate inhibitory capacity critical for maintaining system balance. Given unique immunoregulatory abilities Tregs, targeted therapeutic drugs may position novel immunotherapy. This could restoring balance, resolving dysregulation, fostering innovation progress

Language: Английский

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The aryl hydrocarbon receptor controls IFN-γ-induced immune checkpoints PD-L1 and IDO via the JAK/STAT pathway in lung adenocarcinoma

The Journal of Immunology, Journal Year: 2025, Volume and Issue: unknown

Published: March 3, 2025

While immunotherapy has shown some efficacy in lung adenocarcinoma (LUAD) patients, many respond only partially or not at all. One limitation improving outcomes is the lack of a complete understanding immune checkpoint regulation. Here, we investigated possible link between an environmental chemical receptor implicated cancer and regulation, AhR, known but counterintuitive mediator immunosuppression (interferon (IFN)-γ), regulation two checkpoints (PD-L1 IDO). AhR gene-edited LUAD cell lines, syngeneic mouse model, bulk scRNA sequencing LUADs tumor-infiltrating T cells were used to map out signaling pathway leading from IFN-γ through JAK/STAT, PD-L1, IDO, tumor-mediated immunosuppression. The data demonstrate that: (1) activation JAK/STAT PD-L1 IDO1 up-regulation mediated by murine human cells, (2) AhR-driven induction results production Kynurenine (Kyn), ligand, which likely mediates AhR→IDO1→Kyn→AhR amplification loop, (3) transplantation AhR-knockout long-term tumor immunity most recipients. (4) 23% tumors that do grow so much slower pace than controls exhibit higher densities CD8+ expressing markers immunocompetence, increased activity, cell-cell communication. definitively IFN-γ-induced checkpoint-mediated support targeting context LUAD.

Language: Английский

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