The Dual Blockade of the TIGIT and PD-1/PD-L1 Pathway as a New Hope for Ovarian Cancer Patients

Cancers, Год журнала: 2022, Номер 14(23), С. 5757 - 5757

Опубликована: Ноя. 23, 2022

The prognosis for ovarian cancer (OC) patients is poor and the five-year survival rate only 47%. Immune checkpoints (ICPs) appear to be potential targets in up-and-coming OC treatment. However, response of immunotherapy based on programmed cell death pathway (PD-1/PD-L1) inhibitors totals 6-15%. promising approach a combined therapy, including other ICPs such as T-cell immunoglobulin ITIM domain/CD155/DNAX accessory molecule-1 (TIGIT/CD155/DNAM-1) axis. Preclinical studies murine model colorectal showed that dual blockade PD-1/PD-L1 TIGIT led remission whole studied group vs. regression tumors with single pathway. stimulates effector activity T cells NK cells, redirects immune system against tumor. understanding synergistic action is, however, poor. Thus, aim this review summarize current knowledge about mode its benefits patients. Considering positive impact therapy malignancies, lung cancer, it appears

Язык: Английский

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NKG2A Immune Checkpoint in Vδ2 T Cells: Emerging Application in Cancer Immunotherapy

Cancers, Год журнала: 2023, Номер 15(4), С. 1264 - 1264

Опубликована: Фев. 16, 2023

Immune regulation has revolutionized cancer treatment with the introduction of T-cell-targeted immune checkpoint inhibitors (ICIs). This successful immunotherapy led to a more complete view that now considers not only cells be targeted and destroyed but also environment cells. Current challenges associated enhancement ICI effects are increasing fraction responding patients through personalized combinations multiple ICIs overcoming acquired resistance. requires overview anti-tumor response, which depends on complex interplay between innate adaptive tumor microenvironment. The NKG2A was revealed key for both Natural Killer (NK) T Monalizumab, humanized anti-NKG2A antibody, enhances NK cell activity against various rescues CD8 αβ function in combination PD-1/PD-L1 blockade. In this review, we discuss potential targeting expressed tumor-sensing human γδ cells, mostly specific Vδ2 subset, order emphasize its importance development new ICI-based therapeutic approaches.

Язык: Английский

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Single-cell technologies in multiple myeloma: new insights into disease pathogenesis and translational implications

Biomarker Research, Год журнала: 2023, Номер 11(1)

Опубликована: Май 31, 2023

Multiple myeloma (MM) is a hematological malignancy characterized by clonal proliferation of plasma cells. Although therapeutic advances have been made to improve clinical outcomes and prolong patients' survival in the past two decades, MM remains largely incurable. Single-cell sequencing (SCS) powerful method dissect cellular molecular landscape at single-cell resolution, instead providing averaged results. The application technologies promises address outstanding questions biology has revolutionized our understanding inter- intra-tumor heterogeneity, tumor microenvironment, mechanisms resistance MM. In this review, we summarize recently developed SCS methodologies latest research progress achieved profiling, including information regarding cancer immune cell landscapes, heterogeneities, underlying biomarkers associated with response resistance. We also discuss future directions applying transformative approaches contribution translation.

Язык: Английский

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Tumor‐infiltrating gamma delta T‐cells reveal exhausted subsets with remarkable heterogeneity in colorectal cancer

International Journal of Cancer, Год журнала: 2023, Номер 153(9), С. 1684 - 1697

Опубликована: Авг. 2, 2023

Abstract The γδT‐cells recognize infected or transformed cells. However, unlike αβT‐cells, are innate‐like immune cells, with no major histocompatibility complex restriction requirements. the main population of intestinal intraepithelial lymphocytes (IELs) and associated antitumor response, particularly in colorectal cancer (CRC). Although CD8 + T‐cells exhibit dysfunction even exhaustion tumor microenvironment (TME), which contributes to escape, whether same applies tumor‐infiltrating (TI)‐γδT‐cells is not completely understood. Here, we sought investigate expression pattern inhibitory receptors functional state TI‐γδT‐cells, reveal features exhausted TI‐γδT‐cells CRC TME. We demonstrated that exhibited phenotypes displayed more severe than TI‐CD8 NK‐cells TME CRC. In addition, scRNA‐seq analysis revealed three subsets remarkable heterogeneity. presence heterogeneous γδT‐cell (Tex) populations, including Tex prog , tran term were further confirmed by flow cytometry, on basis PD‐1 TIM‐3 expression. Finally, c‐Maf only contributed via upregulation receptors, but also involved T NK‐cells. may be an important contributor patients. These findings indicated phenotypic provide help for understanding mechanisms association development pathogenesis.

Язык: Английский

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TIM-3 teams up with PD-1 in cancer immunotherapy: mechanisms and perspectives

Molecular Biomedicine, Год журнала: 2025, Номер 6(1)

Опубликована: Май 7, 2025

Abstract Immunotherapy using immune checkpoint inhibitors (ICIs) has become a prominent strategy for cancer treatment over the past ten years. However, efficacy of ICIs remains limited, with certain cancers exhibiting resistance to these therapeutic approaches. Consequently, several proteins are presently being thoroughly screened and assessed in both preclinical clinical studies. Among candidates, T cell immunoglobulin mucin-domain containing-3 (TIM-3) is considered promising target. TIM-3 exhibits multiple immunosuppressive effects on various types cells. Given its differential expression levels at distinct stages dysfunction tumor microenvironment (TME), TIM-3, along programmed death protein 1 (PD-1), serves as indicators exhaustion. Moreover, it crucial carefully evaluate impact PD-1 cells immunotherapy. To increase effectiveness anti-TIM-3 anti-PD-1 therapies, proposed combine inhibition PD-1, death-ligand (PD-L1). The conjunction PD-1/PD-L1 evaluated number ongoing trials patients cancers. This study systematically investigates fundamental biology well detailed mechanisms through which axis contribute evasion. Additionally, this article provides thorough analysis evaluating synergistic combining anti-cancer treatment, an overview current status antibodies.

Язык: Английский

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γδ T cells and the PD-1/PD-L1 axis: a love–hate relationship in the tumor microenvironment

Journal of Translational Medicine, Год журнала: 2024, Номер 22(1)

Опубликована: Июнь 10, 2024

Язык: Английский

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The Variations’ in Genes Encoding TIM-3 and Its Ligand, Galectin-9, Influence on ccRCC Risk and Prognosis

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(3), С. 2042 - 2042

Опубликована: Янв. 20, 2023

Renal cell cancer is the most common type of kidney in adults, and clear renal carcinoma (ccRCC) diagnosed type. T immunoglobulin mucin-domain-containing-3 (TIM-3) belongs to immunological checkpoints that are key regulators immune response. One known TIM-3 ligands galectin-9 (LGALS9). A limited number studies have shown an association between polymorphisms risk Asian population; however, there no study on role LGALS9 cancer. The present aimed analyze influence susceptibility ccRCC patient overall survival (OS), with over ten years observations. Using TaqMan probes, ARMS-PCR, RFPL-PCR, we genotyped two single-nucleotide (SNPs): rs1036199 rs10057302, four SNPs: rs361497, rs3751093, rs4239242, rs4794976. We found presence rs10057302 allele (AC + AA genotypes) as well rs4794976 (GT TT decreased by two-fold compared corresponding homozygotes. subgroup analysis showed some SNPs clinical features. Moreover, significantly influenced OS. Our results indicate variations within genes associated

Язык: Английский

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The role of γδ T cells in the immunopathogenesis of inflammatory diseases: from basic biology to therapeutic targeting

Journal of Leukocyte Biology, Год журнала: 2023, Номер 114(6), С. 557 - 570

Опубликована: Апрель 11, 2023

Abstract The γδ T cells are lymphocytes with an innate-like phenotype that can distribute to different tissues reside and participate in homeostatic functions such as pathogen defense, tissue modeling, response stress. These originate during fetal development migrate the a TCR chain–dependent manner. Their unique manner respond danger signals facilitates initiation of cytokine-mediated diseases spondyloarthritis psoriasis, which immune-mediated very strong link mucosal disturbances, either skin or gut. In spondyloarthritis, one main sources IL-17 and, therefore, drivers inflammation probably new bone formation. Remarkably, this population be bridge between gut joint inflammation.

Язык: Английский

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Vdelta1 T cells are more resistant than Vdelta2 T cells to the immunosuppressive properties of galectin-3

Frontiers in Immunology, Год журнала: 2024, Номер 14

Опубликована: Янв. 8, 2024

Ovarian carcinomas have the highest lethality amongst gynecological tumors. A problem after primary resection is recurrence of epithelial ovarian which often associated with chemotherapy resistance. To improve clinical outcome, it high interest to consider alternative therapy strategies. Due their pronounced plasticity, γδ T cells are attractive for T-cell-based immunotherapy. However, tumors might escape by release lectin galectin-3, impairs T-cell function. Hence, we tested effect galectin-3 on different subsets. After coculture between tumor and Vδ1 or Vδ2 enhanced levels were released. This protein did not affect cytotoxicity both subsets, but differentially influenced proliferation two While increased recombinant inhibited cells, unaffected. In contrast strongly upregulated binding partner α3β1-integrin activation correlating immunosuppressive properties galectin-3. addition, reduced effector memory compartment zoledronate-activated cells. Therefore, our data suggest that an as part a immunotherapy can be advantage.

Язык: Английский

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The Landscape of Adoptive Cellular Therapies in Ovarian Cancer

Cancers, Год журнала: 2023, Номер 15(19), С. 4814 - 4814

Опубликована: Сен. 30, 2023

Ovarian cancers are typically poorly immunogenic and have demonstrated disappointing responses to immune checkpoint inhibitor (ICI) therapy. Adoptive cellular therapy (ACT) offers an alternative method of harnessing the system that has shown promise, especially with success chimeric antigen receptor T-cell (CAR-T) in haematologic malignancies. So far, ACT led modest results treatment solid organ This review explores possibility as effective or additional current standards care ovarian cancer. We will highlight potential ACTs, such CAR-T, (TCR-T), tumour-infiltrating lymphocytes (TILs) cell-based vaccines, whilst also discussing their challenges. present clinical studies for these approaches immunologically 'cold' cancer consider rationale future research.

Язык: Английский

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