Tissue‐resident memory T cells in diseases and therapeutic strategies

MedComm, Journal Year: 2025, Volume and Issue: 6(1)

Published: Jan. 1, 2025

Abstract Tissue‐resident memory T (T RM ) cells are crucial components of the immune system that provide rapid, localized responses to recurrent pathogens at mucosal and epithelial barriers. Unlike circulating cells, located within peripheral tissues, they play vital roles in antiviral, antibacterial, antitumor immunity. Their unique retention activation mechanisms, including interactions with local expression adhesion molecules, enable their persistence immediate functionality diverse tissues. Recent advances have revealed important chronic inflammation, autoimmunity, cancer, illuminating both protective pathogenic potential. This review synthesizes current knowledge on cells’ molecular signatures, maintenance pathways, functional dynamics across different We also explore other such as B macrophages, dendritic highlighting complex network underpins efficacy surveillance response. Understanding nuanced regulation is essential for developing targeted therapeutic strategies, vaccines immunotherapies, enhance while mitigating adverse effects. Insights into biology hold promise innovative treatments infectious diseases, autoimmune conditions.

Language: Английский

---

Single cell profiling of circulating autoreactive CD4 T cells from patients with autoimmune liver diseases suggests tissue imprinting

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: Jan. 29, 2025

Abstract Autoimmune liver diseases (AILD) involve dysregulated CD4 T cell responses against self-antigens, but how these autoreactive cells relate to tissue pathology remains unclear. Here we perform single-cell transcriptomic and receptor analyses of circulating, self-antigen-specific from patients with AILD identify a subset liver-autoreactive distinct B-helper transcriptional profile characterized by PD-1, TIGIT HLA-DR expression. These share clonal relationships expanded intrahepatic exhibit signatures overlapping tissue-resident in chronically inflamed environments. Using mouse model, demonstrate that, following antigen recognition the liver, acquire an exhausted phenotype, play crucial role damage, are controlled immune checkpoint pathways. Our findings thus suggest that circulating imprinted chronic exposure promote inflammation, thereby serving as potential target for developing biomarkers therapies AILD.

Language: Английский

---

Neoadjuvant anti-4-1BB confers protection against spontaneous metastasis through low-affinity intratumor CD8+ T cells in triple-negative breast cancer

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 2, 2025

ABSTRACT Neoadjuvant immunotherapy seeks to harness the primary tumor as a source of relevant antigens enhance systemic anti-tumor immunity through improved immunological surveillance. Despite having revolutionized treatment patients with high-risk early-stage triple-negative breast cancer (TNBC), significant portion remain unresponsive and succumb metastatic recurrence post-treatment. Here, we found that optimally scheduled neoadjuvant administration anti-4-1BB monotherapy was able counteract metastases prolong survival following surgical resection. Phenotypic transcriptional profiling revealed enhanced 4-1BB expression on tumor-infiltrating intermediate (T int ), relative progenitor prog ) terminally exhausted term T cells. Furthermore, enriched in low-affinity Treatment drove clonal expansion , reduced tissue-retention marker CD103 . This accompanied by increased TCR clonotype sharing between paired tumors pre-metastatic lungs. Further interrogation sorted intratumor cells confirmed cell egress into circulation treatment. In addition, gene signature extracted from treated consistently associated clinical outcomes BRCA patients. Combinatorial ablation tumor-derived CXCL16 resulted therapeutic effect. These findings illustrate changes underpinning efficacy anti-4-1BB, highlighting reciprocity local distant immunologic fortification, suggesting can reverse siphoning tumor, enabling redistribution tissues subsequent protection against metastases.

Language: Английский

---

Tissue-resident memory T cells in urinary tract diseases

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

Published: Feb. 24, 2025

Tissue-resident memory T (TRM) cells are a specialized subset of that permanently reside in non-lymphoid tissues, providing localized and long-lasting immune protection. In the urinary tract, TRM play critical roles defending against infections, mediating tumor immunity, influencing pathogenesis chronic inflammatory diseases. Their therapeutic potential is immense, with promising avenues for vaccine development, enhanced cancer immunotherapy, targeted treatments inflammation. However, challenges remain harnessing their protective while minimizing pathological effects, particularly immunosuppressive or microenvironments. This review explores diverse tract diseases, including cancer, inflammation, discusses strategies future directions leveraging to improve clinical outcomes. By advancing our understanding cell biology, we can develop innovative interventions balance immune-protective regulatory functions.

Language: Английский

---

Tissue‐Resident Memory CD8+ T Cells: Differentiation, Phenotypic Heterogeneity, Biological Function, Disease, and Therapy

MedComm, Journal Year: 2025, Volume and Issue: 6(3)

Published: March 1, 2025

ABSTRACT CD8+ tissue‐resident memory T cells (TRM) are strategically located in peripheral tissues, enabling a rapid response to local infections, which is different from circulating cells. Their unique positioning makes them promising targets for vaccines designed enhance protection at barrier sites and other organs. Recent studies have shown correlation between TRM favorable clinical outcomes various types of cancer, indicating their potential role immune checkpoint blockade (ICB) therapies. However, the dual nature presents challenges, as inappropriate activation may lead autoimmunity chronic inflammatory conditions. This review highlights significant advancements field, focusing on differentiation pathways phenotypic heterogeneity across tissues disease states. We also protective roles contexts implications vaccine development against infections treatment strategies tumors. Overall, this comprehensive outlines common features cell biological functions, emphasizing specific characteristics diverse states, can guide design therapies tumors while minimizing risk autoimmune diseases.

Language: Английский

---

KLF2 inhibition expands tumor-resident T cells and enhances tumor immunity

Research Square (Research Square), Journal Year: 2025, Volume and Issue: unknown

Published: March 13, 2025

Tissue resident memory CD8+ T cells (Trm) constitute a distinct population of non-circulating 1-5 vastly exceeding the number circulating 5 , and play pivotal role in protective immunity against pathogens 6-8 . How to promote generation vaccine specific Trm remains an important challenge. Whether contribute also immune control tumors or just correlate with unrelated process linked clinical outcome has not been unequivocally established 9,10 phenotypic markers such as co-expression CD69 CD103 CD49a integrins commonly used monitor tumor infiltrating do unambiguously define this subset. Here we tested hypothesis that transient downregulation KLF2, most conserved feature ontogeny 4,11,12 will differentiation activated into enhance antitumor immunity. We show 4-1BB antibody targeted delivery KLF2 siRNA bearing mice led accumulation phenotypically defined intratumoral CD69+CD103+ CD69+CD49a+ which correlated enhanced growth. This study could serve foundation broadly applicable clinically useful way provides direct evidence CD8+CD69+CD103+ CD8+CD69+CD49a+ are indeed

Language: Английский

---

An Injectable Gambogic Acid Loaded Nanocomposite Hydrogel Enhances Antitumor Effect by Reshaping Immunosuppressive Tumor Microenvironment

Materials Today Bio, Journal Year: 2025, Volume and Issue: 31, P. 101611 - 101611

Published: Feb. 24, 2025

Language: Английский

---

Differentiation of Cytotoxic CD8⁺ T Cell Subsets Under Tumor Progression: Can CD69 Be a New Therapeutic Target?

Cancer Science, Journal Year: 2025, Volume and Issue: unknown

Published: March 25, 2025

Tumor-specific CD8+ T cells play a pivotal role in anti-tumor immunity. Here, we review the heterogeneity of cell subsets during tumor progression. While both acute and chronic viral infections induce distinct responses, responses are also observed development. Chronic immune have traditionally been considered to represent dysfunctional state cells, whereas identification TCF1+ stem-like has highlighted their importance During progression, differentiate into cytotoxic Tim-3+ terminally differentiated through mechanisms that remain largely unknown. We recently identified CD69 as an important regulator showed blocking function, either administration anti-CD69 antibody (Ab) or genetic knockout, enhanced generation tumor-draining lymph nodes (TDLNs) microenvironment (TME), thereby enhancing response. These findings suggest is attractive therapeutic target controls

Language: Английский

---

Case report: Partial regression of metastatic squamous cell carcinoma with altered azathioprine dosage after long-term use in renal transplant patient

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: Oct. 31, 2024

We report the partial regression of metastatic squamous cell carcinoma (SCC) after reduction long-term azathioprine therapy while awaiting surgery. The patient was a 69-year-old man with history kidney transplantation. Moderately differentiated SCC arising in anterior neck initially diagnosed, followed later by poorly metastases to cervical lymph nodes. Lymph node clearance performed 28 days dosage. palpable lesion had noticeably decreased size at time surgery, and subsequent histology only detected 7mm 0.2mm deposits 2 5 level I nodes, further 10 reactive nodes from levels II III. One positive another benign II/III node, demonstrated necrosis, histiocytic infiltration fibrosis, interpreted as features regression. Hence, we investigated role immune cells

Language: Английский

---