Current Understanding of Hypoxia in Glioblastoma Multiforme and Its Response to Immunotherapy

Cancers, Journal Year: 2022, Volume and Issue: 14(5), P. 1176 - 1176

Published: Feb. 24, 2022

Hypoxia is a hallmark of glioblastoma multiforme (GBM), the most aggressive cancer central nervous system, and associated with multiple aspects tumor pathogenesis. For example, hypoxia induces resistance to conventional therapies inhibits antitumor immune responses. Thus, targeting an attractive strategy for GBM therapy. However, traditional studies on have largely excluded system. Recently, critical role system in defense against tumors has become apparent, leading development effective immunotherapies numerous types. Critically, however, classified as “cold tumor” due poor improve responsiveness immunotherapies, improved understanding both function mediating responses within microenvironment needed. In this review, we discuss from clinical, pathological, immunological perspective.

Language: Английский

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New immune cell engagers for cancer immunotherapy

Nature reviews. Immunology, Journal Year: 2024, Volume and Issue: 24(7), P. 471 - 486

Published: Jan. 25, 2024

Language: Английский

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The Role of Vitamin D and Vitamin D Binding Protein in Chronic Liver Diseases

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(18), P. 10705 - 10705

Published: Sept. 14, 2022

Vitamin D (calciferol) is a fat-soluble vitamin that has significant role in phospho-calcium metabolism, maintaining normal calcium levels and bone health development. The most important compounds of are cholecalciferol (vitamin D3, or VD3) ergocalciferol D2, VD2). Besides its major an adequate level phosphate concentrations, involved cell growth differentiation immune function. Recently, the association between deficiency progression fibrosis chronic liver disease (CLD) was confirmed, given hepatic activation process high prevalence these diseases. There reports CLD regardless etiology (chronic viral hepatitis, alcoholic cirrhosis, non-alcoholic fatty disease, primary biliary autoimmune hepatitis). binding protein (VDBP) synthesized by transporting metabolites to target organs. VDBP also plays inflammatory response secondary tissue damage, being degradation actin. As intense research during last decades revealed possible diseases, deeper understanding D, receptors (VDRs), involvement inflammation fibrogenesis could represent basis for development new strategies diagnosis, prognosis, treatment This narrative review presents overview evidence CLD, both at experimental clinical levels.

Language: Английский

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γδ T Cells in the Tumor Microenvironment—Interactions With Other Immune Cells

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

Published: July 8, 2022

A growing number of studies have shown that γδ T cells play a pivotal role in mediating the clearance tumors and pathogen-infected with their potent cytotoxic, cytolytic, unique immune-modulating functions. Unlike more abundant αβ cells, can recognize broad range infected without requirement antigen presentation via major histocompatibility complex (MHC) molecules. Our group has recently demonstrated parts mechanisms T-cell receptor (TCR)-dependent activation Vγ9Vδ2+ by following phosphoantigens, intermediates mevalonate pathway. This process is mediated through B7 immunoglobulin family-like butyrophilin 2A1 (BTN2A1) BTN3A1 complexes. Such recognition results activation, robust immunosurveillance process, elicits rapid immune responses. These include targeted cell killing, ability to produce copious quantities cytokines chemokines exert properties interact other cells. network includes B dendritic macrophages, monocytes, natural killer neutrophils, hence heavily influencing outcome key orchestrating tropism for tumor microenvironment makes an attractive target cancer immunotherapy. Here, we review current understanding these important interactions highlight implications crosstalk between context anti-tumor immunity.

Language: Английский

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New cell sources for CAR-based immunotherapy

Biomarker Research, Journal Year: 2023, Volume and Issue: 11(1)

Published: May 6, 2023

Chimeric antigen receptor (CAR) T cell therapy, in which a patient's own lymphocytes are engineered to recognize and kill cancer cells, has achieved striking success some hematological malignancies preclinical clinical trials, resulting six FDA-approved CAR-T products currently available the market. Despite impressive outcomes, concerns about treatment failure associated with low efficacy or high cytotoxicity of cells remain. While main focus been on improving exploring alternative cellular sources for CAR generation garnered growing interest. In current review, we comprehensively evaluated other rather than conventional generation.

Language: Английский

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Multiomics profiling reveals the benefits of gamma-delta (γδ) T lymphocytes for improving the tumor microenvironment, immunotherapy efficacy and prognosis in cervical cancer

Journal for ImmunoTherapy of Cancer, Journal Year: 2024, Volume and Issue: 12(1), P. e008355 - e008355

Published: Jan. 1, 2024

As an unconventional subpopulation of T lymphocytes, γδ cells can recognize antigens independently major histocompatibility complex restrictions. Recent studies have indicated that play contrasting roles in tumor microenvironments-promoting progression some cancers (eg, gallbladder and leukemia) while suppressing it others lung gastric). are mainly enriched peripheral mucosal tissues. the cervix is a mucosa-rich tissue, role cervical cancer warrants further investigation.

Language: Английский

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Advancements in γδT cell engineering: paving the way for enhanced cancer immunotherapy

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

Published: March 21, 2024

Comprising only 1-10% of the circulating T cell population, γδT cells play a pivotal role in cancer immunotherapy due to their unique amalgamation innate and adaptive immune features. These can secrete cytokines, including interferon-γ (IFN-γ) tumor necrosis factor-α (TNF-α), directly eliminate through mechanisms like Fas/FasL antibody-dependent cell-mediated cytotoxicity (ADCC). Unlike conventional αβT cells, target wide variety independently major histocompatibility complex (MHC) presentation function as antigen-presenting (APCs). Their ability recognizing antigens non-MHC restricted manner makes them an ideal candidate for allogeneic immunotherapy. Additionally, exhibit specific tissue tropism, rapid responsiveness upon reaching cellular targets, indicating high level precision adaptability. Despite these capabilities, therapeutic potential has been hindered by some limitations, abundance, unsatisfactory expansion, limited persistence, biology plasticity. To address issues, gene-engineering strategies use chimeric antigen receptor (CAR) therapy, (TCR) gene transfer, combination with engagers are being explored. This review will outline progress various engineering strategies, discuss implications challenges that lie ahead, future directions engineered both monotherapy

Language: Английский

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Payload-delivering engineered γδ T cells display enhanced cytotoxicity, persistence, and efficacy in preclinical models of osteosarcoma

Science Translational Medicine, Journal Year: 2024, Volume and Issue: 16(749)

Published: May 29, 2024

T cell–based cancer immunotherapy has typically relied on membrane-bound cytotoxicity enhancers such as chimeric antigen receptors expressed in autologous αβ cells. These approaches are limited by tonic signaling of synthetic constructs and costs associated with manufacturing. γδ cells an emerging alternative for cellular therapy, having innate antitumor activity, potent antibody-dependent cytotoxicity, minimal alloreactivity. We present immunotherapeutic platform technology built around the properties Vγ9Vδ2 cell, harnessing specific characteristics this cell type offering allocompatible therapy that recruits bystander immunity. engineered to secrete tumor-targeting opsonins form scFv-Fc fusion protein a mitogenic IL-15Rα–IL-15 (stIL15). Using GD2 model antigen, we show GD2-specific opsonin-secreting (stIL15-OPS-γδ cells) have enhanced promote activity other lymphoid myeloid Secretion stIL-15 abrogated need exogenous cytokine supplementation further mediated activation natural killer Compared unmodified cells, stIL15-OPS-γδ exhibited superior vivo control subcutaneous tumors persistence blood. Moreover, were efficacious against patient-derived osteosarcomas animal models vitro, where efficacy could be boosted addition zoledronic acid. Together, data identify candidate allogeneic combining direct cytolysis tumor control.

Language: Английский

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Tissue-Specific Expression of TIGIT, PD-1, TIM-3, and CD39 by γδ T Cells in Ovarian Cancer

Cells, Journal Year: 2022, Volume and Issue: 11(6), P. 964 - 964

Published: March 11, 2022

Phenotypic characterization of γδ T cells in the MALs (malignant ascites lymphocytes), TILs (tumor infiltrating and PBLs (peripheral blood lymphocytes) ovarian cancer (OvCA) patients is lacking. Therefore, we quantified cell prevalence MAL, TIL, PBL specimens from n = 18 OvCA age-matched healthy donors (HD, 14). Multicolor flow cytometry was performed to evaluate expression inhibitory receptors (TIGIT, PD-1 TIM-3), stimulatory (Ox40), purinergic ectoenzymes (CD39 CD73) on subsets. We identified an abundant infiltration Vδ1 TILs. These varied their differentiation: The majority displayed effector memory (EM) phenotype, whereas had a more mature phenotype terminally differentiated (TEMRA) with high CD45RA expression. TIGIT TIM-3 were abundantly expressed both PBLs, exhibited highest levels PD-1, CD39, Ox40. also observed specific clusters differentiation stages for analyzed molecules. Regarding co-expression, showed co-expressing or CD39 compared PBLs. In conclusion, population primary tumors patients. Due (co-)expression targetable immune receptors, particular TILs, cell-based approaches combined inhibition these targets might represent promising strategy OvCA.

Language: Английский

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Human γδ T Cell Subsets and Their Clinical Applications for Cancer Immunotherapy

Cancers, Journal Year: 2022, Volume and Issue: 14(12), P. 3005 - 3005

Published: June 18, 2022

Gamma delta (γδ) T cells are a minor population of that share adaptive and innate immune properties. In contrast to MHC-restricted alpha beta (αβ) cells, γδ activated in an MHC-independent manner, making them ideal candidates for developing allogeneic, off-the-shelf cell-based immunotherapies. As the field cancer immunotherapy progresses rapidly, different subsets have been explored. addition, can be engineered using gene editing technologies augment their tumor recognition abilities antitumor functions. this review, we outline unique features human We also summarize past ongoing pre-clinical studies clinical trials utilizing immunotherapy.

Language: Английский

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