Can invariant Natural Killer T cells drive B cell fate? a look at the humoral response

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

Published: Feb. 18, 2025

Invariant Natural Killer T (NKT) cells represent a unique subset of innate-like that express both NK cell and receptors. These are rapidly activated by glycolipid antigens presented via CD1d molecules on antigen-presenting (APCs), including B cells, dendritic (DCs), macrophages, or through cytokine-dependent mechanisms. Their ability to produce wide range cytokines costimulatory underscores their critical role in bridging innate adaptive immunity. traditionally recognized for antibody production, also act as potent APCs due high expression CD1d, enabling direct interactions with iNKT cells. This interaction has significant implications humoral immunity, influencing activation, class-switch recombination (CSR), germinal center formation, memory differentiation, thus expanding the conventional paradigm cell-B interactions. While influence biology responses is well-supported, many aspects remain unresolved. Key questions include roles different subsets, diversity APCs, spatiotemporal dynamics these interactions, especially during early potential distinct ligands modulate immune outcomes. Understanding factors could provide valuable insights into how regulate cell-mediated immunity offer opportunities harness immunotherapeutic applications, such vaccine development. In this review, we examine unresolved propose novel perspective regulatory emphasizing promise target innovative strategies.

Language: Английский

---

Rationally Designed Highly Potent NKT Cell Agonists with Different Cytokine Selectivity through Hydrogen-Bond Interaction

Journal of Medicinal Chemistry, Journal Year: 2024, Volume and Issue: 67(15), P. 12819 - 12834

Published: July 20, 2024

Synthetic α-galactosylceramide (αGalCer) and its analogues as powerful agonists for natural killer T (NKT) cell manipulation have received significant attention in immunotherapy adjuvant development. However, identifying new potent NKT agonists, especially those with Th1 selectivity that promote anticancer effects, remains a challenging task. In this work, we introduced sulfonamide group into the acyl chain of αGalCer to form additional hydrogen bonds intensify glycolipid/CD1d interaction. Two compounds

Language: Английский

---

Patient-Derived Organoid Models for NKT Cell-Based Cancer Immunotherapy

Cancers, Journal Year: 2025, Volume and Issue: 17(3), P. 406 - 406

Published: Jan. 26, 2025

Invariant Natural Killer T (iNKT) cells are a unique subset of that bridge innate and adaptive immunity, displaying potent anti-tumor properties through cytokine secretion, direct cytotoxicity, recruitment immune effector such as CD8+ NK cells. Despite their therapeutic potential, the immunosuppressive tumor microenvironment (TME), characterized by regulatory cells, myeloid-derived suppressor (MDSCs), tumor-associated macrophages (TAMs), limits iNKT cell efficacy. Patient-derived organoid (PDO) platforms provide an innovative model for dissecting these complex interactions evaluating strategies to reinvigorate functionality within TME. PDOs closely mimic genetic, phenotypic, structural characteristics primary tumors, enabling study tumor–immune dynamics. Integrating into offers robust platform investigating CD1d-mediated interactions, Th1-biased responses driven glycolipid analogs like α-GalCer, combination therapies checkpoint inhibitors. Additionally, PDO systems can assess effects metabolic modulation, including reducing lactic acid accumulation or targeting glutamine pathways, on enhancing activity. Emerging innovations, organoid-on-a-chip systems, CRISPR-Cas9 gene editing, multi-omics approaches, further expand potential PDO–iNKT personalized immunotherapy research. Although application in is still undeveloped, hold immense promise bridging preclinical studies clinical translation. By addressing challenges TME optimizing strategies, offer transformative avenue advancing cancer medicine.

Language: Английский

---

Tumor-Associated Macrophages: Polarization, Immunoregulation, and Immunotherapy

Cells, Journal Year: 2025, Volume and Issue: 14(10), P. 741 - 741

Published: May 19, 2025

Tumor-associated macrophages’ (TAMs) origin, polarization, and dynamic interaction in the tumor microenvironment (TME) influence cancer development. They are essential for homeostasis, monitoring, immune protection. Cells from bone marrow or embryonic progenitors dynamically polarize into pro- anti-tumor M2 M1 phenotypes based on cytokines metabolic signals. Recent advances TAM heterogeneity, characterization, immunological responses, therapy described here. The manuscript details functions their role resistance to PD-1/PD-L1 blockade. Similarly, TAM-targeted approaches, such as CSF-1R inhibition PI3Kγ-driven reprogramming, discussed address immunity suppression. Furthermore, innovative biomarkers combination may enhance TAM-centric therapies. It also stresses relevance of this distinct cell human health disease, which could impact future research

Language: Английский

---

Diphtheria Toxoid-Derived T-Helper Epitope and α-galactosylceramide Synergistically Enhance the Immunogenicity of Glycopeptide Antigen

ACS Pharmacology & Translational Science, Journal Year: 2024, Volume and Issue: 7(12), P. 3889 - 3901

Published: Nov. 4, 2024

The tumor-associated antigen MUC1 is an attractive target for immunotherapy, however, its weak immunogenicity limits the induction of antitumor immune responses. To overcome this limitation, in study, glycopeptide was covalently linked with a diphtheria toxin-derived T-helper epitope (DT331–345). Subsequently, resulting DT-MUC1 physically mixed natural killer T cell agonist αGalCer to explore their immunomodulatory synergy. Biological results demonstrated that compared MUC1+αGalCer and groups, specific IgG antibody titer DT-MUC1+αGalCer group increased by 189- 3-fold, respectively, indicating synergistically enhanced αGalCer. Moreover, vaccine induced potent cellular responses significantly inhibited growth B16-MUC1 tumors vivo. Furthermore, it found anti-MUC1 equivalent palmitoylated (P1-DT-MUC1+αGalCer) higher than doubly (P2-DT-MUC1+αGalCer), suggesting easily synthesized may not require lipid chain modification already possess good amphiphilicity. This first time helper enhance immunogenicity, study provide effective design strategy MUC1-targeted vaccines offer novel insights into fully synthetic peptide vaccines.

Language: Английский

---

Optimizing iNKT-driven immune responses against cancer by modulating CD1d in tumor and antigen presenting cells

Clinical Immunology, Journal Year: 2024, Volume and Issue: 269, P. 110402 - 110402

Published: Nov. 17, 2024

Language: Английский

---

Testing Green Tea Extract and Ammonium Salts as Stimulants of Physical Performance in a Forced Swimming Rat Experimental Model

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(19), P. 10438 - 10438

Published: Sept. 27, 2024

The study of drugs natural origin that increase endurance and/or accelerate recovery is an integral part sports medicine and physiology. In this paper, decaffeinated green tea extract (GTE) two ammonium salts-chloride (ACL) carbonate (ACR)-were tested individually in combination with GTE as stimulants physical performance a forced swimming rat experimental model. determined parameters can be divided into seven blocks: functional (swimming duration); biochemistry blood plasma; erythrocytes; hematology; immunology; gene expression slow- fast-twitch muscles (m. soleus, SOL, m. extensor digitorum longus, EDL, respectively); morphometric indicators muscles. Regarding the negative control (intact animals), maximum number changes all blocks was recorded + ACR group, whose animals showed result minimum lactate values on last day experiment. Next, terms changes, were groups ACR, ACL, NaCl (positive control). general, identified adaptive proportional to state corresponding groups, duration load four days However, not only total but also qualitative composition interest. results comparative analysis suggest that, model we developed, promotes restoration body moderate mobilization immune system, while small doses salts, especially carbonate, contribute performance, which associated satisfactory skeletal entire body. combined use salts does give clearly positive effect.

Language: Английский

---

Characterization of Tissue Immunity Defense Factors of the Lip in Primary Dentition Children with Bilateral Cleft Lip Palate

Journal of Personalized Medicine, Journal Year: 2024, Volume and Issue: 14(9), P. 965 - 965

Published: Sept. 11, 2024

Bilateral cleft lip palate is a severe congenital birth defect of the mouth and face. Immunity factors modulate immune response, inflammation, healing; therefore, they are vital in assessment immunological status patient. The aim this study to assess distribution Gal-10, CD-163, IL-4, IL-6, IL-10, HBD-2, HBD-3, HBD-4 tissue bilateral primary dentition children.

Language: Английский

---

Synthesis of Spin-Labeled α-/β-Galactosylceramides and Glucosylceramides as Electron Paramagnetic Probes

The Journal of Organic Chemistry, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 16, 2024

α-/β-Galactosylceramide (GalCer) and glucosylceramide (GlcCer) derivatives having a radical label at the 6-

Language: Английский

---