Dendritic cells as orchestrators of anticancer immunity and immunotherapy

Nature Reviews Clinical Oncology, Год журнала: 2024, Номер 21(4), С. 257 - 277

Опубликована: Фев. 7, 2024

Язык: Английский

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Co-inhibition of TIGIT and PD-1/PD-L1 in Cancer Immunotherapy: Mechanisms and Clinical Trials

Molecular Cancer, Год журнала: 2023, Номер 22(1)

Опубликована: Июнь 8, 2023

Abstract Over the past decade, immune checkpoint inhibitors (ICIs) have emerged as a revolutionary cancer treatment modality, offering long-lasting responses and survival benefits for substantial number of patients. However, response rates to ICIs vary significantly among individuals types, with notable proportion patients exhibiting resistance or showing no response. Therefore, dual ICI combination therapy has been proposed potential strategy address these challenges. One targets is TIGIT, an inhibitory receptor associated T-cell exhaustion. TIGIT diverse immunosuppressive effects on immunity cycle, including inhibition natural killer cell effector function, suppression dendritic maturation, promotion macrophage polarization M2 phenotype, differentiation T cells regulatory cells. Furthermore, linked PD-1 expression, it can synergize PD-1/PD-L1 blockade enhance tumor rejection. Preclinical studies demonstrated co-inhibition in enhancing anti-tumor improving outcomes several types. Several clinical trials are underway evaluate safety efficacy various results awaited. This review provides overview mechanisms treatment, summarizes latest investigating this therapy, discusses its prospects. Overall, represents promising therapeutic approach that improve treated ICIs.

Язык: Английский

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Mature dendritic cells enriched in immunoregulatory molecules (mregDCs): A novel population in the tumour microenvironment and immunotherapy target

Clinical and Translational Medicine, Год журнала: 2023, Номер 13(2)

Опубликована: Фев. 1, 2023

Abstract Background Dendritic cells (DCs) mediate divergent immune effects by activating T or negatively regulating the response to promote tolerance. They perform specific functions determined their tissue distribution and maturation state. Traditionally, immature semimature DCs were described have immunosuppressive effects, leading Nonetheless, recent research has demonstrated that mature can also suppress under certain circumstances. Main body Mature enriched in immunoregulatory molecules (mregDCs) emerged as a regulatory module across species tumour types. Indeed, distinct roles of mregDCs immunotherapy sparked interest researchers field single‐cell omics. In particular, these found be associated with positive favourable prognosis. Conclusion Here, we provide general overview latest most notable advances findings regarding basic features complex nonmalignant diseases microenvironment. We emphasise important clinical implications tumours.

Язык: Английский

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Lymphatic-localized Treg-mregDC crosstalk limits antigen trafficking and restrains anti-tumor immunity

Cancer Cell, Год журнала: 2024, Номер 42(8), С. 1415 - 1433.e12

Опубликована: Июль 18, 2024

Язык: Английский

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Dendritic cell maturation in cancer

Nature reviews. Cancer, Год журнала: 2025, Номер unknown

Опубликована: Фев. 7, 2025

Язык: Английский

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Impaired function of dendritic cells within the tumor microenvironment

Frontiers in Immunology, Год журнала: 2023, Номер 14

Опубликована: Июнь 27, 2023

Dendritic cells (DCs), a class of professional antigen-presenting cells, are considered key factors in the initiation and maintenance anti-tumor immunity due to their powerful ability present antigen stimulate T-cell responses. The important role DCs controlling tumor growth mediating potent has been demonstrated various cancer models. Accordingly, infiltration stimulatory positively correlates with prognosis response immunotherapy variety solid tumors. However, accumulating evidence indicates that exhibit significantly dysfunctional state, ultimately leading an impaired immune effects immunosuppressive microenvironment (TME). Currently, numerous preclinical clinical studies exploring immunotherapeutic strategies better control tumors by restoring or enhancing activity tumors, such as popular DC-based vaccines. In this review, overview progression is provided, followed summary current advances understanding mechanisms which TME affects normal function DCs, concluding brief discussion for immunotherapy.

Язык: Английский

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Single-cell RNA sequencing reveals the cellular and molecular heterogeneity of treatment-naïve primary osteosarcoma in dogs

Communications Biology, Год журнала: 2024, Номер 7(1)

Опубликована: Апрель 24, 2024

Abstract Osteosarcoma (OS) is a heterogeneous, aggressive malignancy of the bone that disproportionally affects children and adolescents. Therapeutic interventions for OS are limited, which in part due to complex tumor microenvironment (TME). As such, we used single-cell RNA sequencing (scRNA-seq) describe cellular molecular composition TME 6 treatment-naïve dogs with spontaneously occurring primary OS. Through analysis 35,310 cells, identified 41 transcriptomically distinct cell types including characterization follicular helper T mature regulatory dendritic cells (mregDCs), 8 tumor-associated macrophage (TAM) populations. Cell-cell interaction predicted mregDCs TAMs play key roles modulating mediated immunity. Furthermore, completed cross-species type gene signature homology found high degree similarity between human canine The data presented here act as roadmap can be applied advance translational immuno-oncology research.

Язык: Английский

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The tumor microenvironment and dendritic cells: Developers of pioneering strategies in colorectal cancer immunotherapy?

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, Год журнала: 2025, Номер 1880(2), С. 189281 - 189281

Опубликована: Фев. 8, 2025

Язык: Английский

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Antigen presenting cells in cancer immunity and mediation of immune checkpoint blockade

Clinical & Experimental Metastasis, Год журнала: 2024, Номер 41(4), С. 333 - 349

Опубликована: Янв. 23, 2024

Abstract Antigen-presenting cells (APCs) are pivotal mediators of immune responses. Their role has increasingly been spotlighted in the realm cancer immunology, particularly as our understanding immunotherapy continues to evolve and improve. There is growing evidence that these play a non-trivial immunity have roles dependent on surface markers, growth factors, transcription their surrounding environment. The main dendritic cell (DC) subsets found conventional DCs (cDC1 cDC2), monocyte-derived (moDC), plasmacytoid (pDC), mature regulatory (mregDC). notable monocytes macrophages include classical non-classical monocytes, macrophages, which demonstrate continuum from pro-inflammatory (M1) phenotype an anti-inflammatory (M2) phenotype, tumor-associated (TAMs). Despite classification same type, each subset may take immune-activating or immunosuppressive shaped by factors tumor microenvironment (TME). In this review, we introduce DCs, recent studies investigating them context. Additionally, review how certain characteristics such abundance, indirect direct signaling pathways influence response checkpoint blockade (ICB) therapy. We also highlight existing knowledge gaps regarding precise contributions different myeloid influencing ICB These findings provide summary current mediating offer insight into alternative combination therapies enhance success cancers.

Язык: Английский

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Vax-Innate: improving therapeutic cancer vaccines by modulating T cells and the tumour microenvironment

Nature reviews. Immunology, Год журнала: 2024, Номер unknown

Опубликована: Окт. 21, 2024

Язык: Английский

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