Differential Infiltration of T-Cell Populations in Tumor and Liver Tissues Predicts Recurrence-Free Survival in Surgically Resected Hepatocellular Carcinoma DOI Open Access

Eun Ji Jang,

Ho Joong Choi,

Young Kyoung You

et al.

Cancers, Journal Year: 2025, Volume and Issue: 17(9), P. 1548 - 1548

Published: May 2, 2025

Background/Objectives: Liver and tumor-infiltrating T cells in hepatocellular carcinoma (HCC) are heterogeneous, comprising the CD69+ tissue-resident T-cell CD69− circulating populations. However, impact of these distinct populations on patient prognosis is unclear; hence, further studies needed. Methods: Tumor distant liver tissues from 57 HCC patients with various chronic disease etiologies were analyzed. Single-cell dissociation flow cytometry used to assess their correlation recurrence-free survival (RFS). Results: CD69+/CD69− subpopulations within CD4+ CD8+ varied by alcohol etiology. among less frequent both tumor non-tumor alcohol-related (p < 0.05). Higher frequencies CD69−CD4+ tumors CD69+CD103+CD8+ associated better RFS. CD69- expressed lower PD-1 levels, indicating exhaustion, expression inversely correlated frequency. was higher HCC. Conclusions: We provided a detailed analysis heterogeneous characteristics tumor- liver-infiltrating HCC, emphasizing roles cell immune exhaustion aggressiveness, whereas appeared significantly contribute influence intake landscape microenvironment. research should validate findings larger cohorts enhance our understanding.

Language: Английский

CD8+ T cells in the cancer-immunity cycle DOI Creative Commons
Josephine R. Giles, Anna-Maria Globig,

Susan M. Kaech

et al.

Immunity, Journal Year: 2023, Volume and Issue: 56(10), P. 2231 - 2253

Published: Oct. 1, 2023

Language: Английский

Citations

161
The tissue-resident regulatory T cell pool is shaped by transient multi-tissue migration and a conserved residency program DOI Creative Commons
Oliver T. Burton, Orian Bricard, Samar Tareen

et al.

Immunity, Journal Year: 2024, Volume and Issue: 57(7), P. 1586 - 1602.e10

Published: June 18, 2024

The tissues are the site of many important immunological reactions, yet how immune system is controlled at these sites remains opaque. Recent studies have identified Foxp3

Language: Английский

Citations

27
RNA neoantigen vaccines prime long-lived CD8+ T cells in pancreatic cancer DOI Creative Commons
Zachary Sethna, Pablo Guasp, Charlotte Reiche

et al.

Nature, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 19, 2025

Language: Английский

Citations

9
GZMK-expressing CD8+ T cells promote recurrent airway inflammatory diseases DOI Creative Commons
Feng Lan, Jizhou Li,

Wenxuan Miao

et al.

Nature, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 15, 2025

Inflammatory diseases are often chronic and recurrent, current treatments do not typically remove underlying disease drivers1. T cells participate in a wide range of inflammatory such as psoriasis2, Crohn's disease3, oesophagitis4 multiple sclerosis5,6, clonally expanded antigen-specific may contribute to chronicity recurrence, part by forming persistent pathogenic memory. Chronic rhinosinusitis asthma airway that present comorbidities7. affects more than 10% the general population8. Among these patients, 20–25% would develop nasal polyps, which require repeated surgical resections owing high incidence recurrence9. Whereas abundant infiltrate polyps tissue10,11, cell subsets drive pathology promote recurrence fully understood. By comparing repertoires polyp tissues obtained from consecutive surgeries, here we report CD8+ clones carrying effector memory-like features colonize mucosal tissue during characteristically express tryptase Granzyme K (GZMK). We find GZMK cleaves many complement components, including C2, C3, C4 C5, collectively activation cascade. GZMK-expressing organized tertiary lymphoid structures, levels predict severity comorbidities better well-established biomarkers eosinophilia interleukin-5. Using mouse model, further show exacerbate manner dependent on proteolytic activity complements. Genetic ablation or pharmacological inhibition after onset markedly alleviates restores lung function. Our work identifies memory subset promotes inflammation recurrent molecule suggests potential therapeutic target. Comparing surgeries shows producing K, complement-activating tryptase, is

Language: Английский

Citations

7
KLF2 maintains lineage fidelity and suppresses CD8 T cell exhaustion during acute LCMV infection DOI
Eric Fagerberg, John Attanasio, Christine Dien

et al.

Science, Journal Year: 2025, Volume and Issue: 387(6735)

Published: Jan. 2, 2025

Naïve CD8 T cells have the potential to differentiate into a spectrum of functional states during an immune response. How these developmental decisions are made and what mechanisms exist suppress differentiation toward alternative fates remains unclear. We employed in vivo CRISPR-Cas9–based perturbation sequencing assess role ~40 transcription factors (TFs) epigenetic modulators cell fate decisions. Unexpectedly, we found that knockout TF Klf2 resulted aberrant exhausted-like acute infection. KLF2 was required exhaustion-promoting TOX enable TBET drive effector differentiation. also necessary maintain polyfunctional tumor-specific progenitor state. Thus, provides lineage fidelity suppresses exhaustion program.

Language: Английский

Citations

2
Metal-Phenolic Vehicles Potentiate Cycle-Cascade Activation of Pyroptosis and cGAS-STING Pathway for Tumor Immunotherapy DOI

Weikai Sun,

Hong Wang, Yafei Qi

et al.

ACS Nano, Journal Year: 2024, Volume and Issue: 18(34), P. 23727 - 23740

Published: Aug. 19, 2024

The treatment of triple-negative breast cancer (TNBC) faces challenges due to its limited immune response and weak tumor immunogenicity. A collaborative strategy involves combining the activation pyroptosis stimulator interferon genes (STING) pathway enhance immunogenicity fortify antitumor response, which may improve therapeutic outcomes in TNBC. In this study, we report fabrication a zinc-phenolic nanocapsule (RMP@Cap), is loaded with mitoxantrone (MTO) anti-PD-L1 antibodies (aPD-L1) coated erythrocyte membrane, for TNBC immunotherapy. delivery RMP@Cap can induce cell and, therefore, trigger release mitochondrial DNA, further combines zinc agonists intensify STING activation, resulting cascade amplification effect on tumors. Additionally, incorporation aPD-L1 into relieves inhibitory cells recruited cytotoxic T cells, thereby improving tumor-killing capacity. Furthermore, camouflaged membrane coating enables nanocapsules achieve prolonged

Language: Английский

Citations

13
Resident memory T cells and cancer DOI
Noah Veis Gavil,

Katarina Cheng,

David Masopust

et al.

Immunity, Journal Year: 2024, Volume and Issue: 57(8), P. 1734 - 1751

Published: Aug. 1, 2024

Language: Английский

Citations

9
T1‐T2 Interplay in the Complex Immune Landscape of Severe Asthma DOI Creative Commons
Marc A. Gauthier,

Sagar Kale,

Anuradha Ray

et al.

Immunological Reviews, Journal Year: 2025, Volume and Issue: 330(1)

Published: Feb. 24, 2025

Asthma is orchestrated by an aberrant immune response involving a complex interplay between multiple inflammatory cell types. An increase in Th2 cells the asthmatic airway hallmark of asthma, and biologics blocking their effector functions have been life-changing for many severe asthma patients who poorly respond to immunosuppression corticosteroids. However, studies past decade highlighted not only other types that also produce cytokines boosting Type 2/T2 phenotype but heightened IFN-γ response, primarily from T cells, referred as 1/T1 response. Data derived airways mouse models suggest role corticosteroid resistance, hyperreactivity, remodeling via effects on including mast eosinophils, epithelial smooth muscle cells. The simultaneous presence T1 T2 responses detectable sickest whom corticosteroids suppress This article has reviewed our current understanding T1-T2 highlighting mediators impact both arms which may be targeted alone or combination disease alleviation.

Language: Английский

Citations

1
Stage-dependent immunity orchestrates AQP4 antibody-guided NMOSD pathology: a role for netting neutrophils with resident memory T cells in situ DOI

Akihiro Nakajima,

Fumihiro Yanagimura, Etsuji Saji

et al.

Acta Neuropathologica, Journal Year: 2024, Volume and Issue: 147(1)

Published: April 24, 2024

Language: Английский

Citations

6
The tissue-resident regulatory T cell pool is shaped by transient multi-tissue migration and a conserved residency program DOI Open Access
Oliver T. Burton, Orian Bricard, Samar Tareen

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Aug. 14, 2023

Abstract The tissues are the site of many most important immunological reactions, yet immunology has remained relatively opaque. Recent studies have identified Foxp3 + regulatory T cells (Tregs) in several non-lymphoid tissues. These tissue-resident populations been ascribed unique characteristics based on comparisons to lymphoid Tregs. Here we performed a systematic analysis Treg population residing organs throughout body, revealing shared phenotypes, transient residency and common molecular dependencies. Further, tissue Tregs from different cell receptor (TCR) sequences, with functional capacity drive multi-tissue entry. Finally, extracted were tissue-agnostic re-entry, without homing preference for their origin. Together these results demonstrate that pool organs, other than gut, is largely constituted by broadly self-reactive Tregs, characterised migration program.

Language: Английский

Citations

13