Targeting of TAMs: can we be more clever than cancer cells?

Cellular and Molecular Immunology, Год журнала: 2024, Номер 21(12), С. 1376 - 1409

Опубликована: Ноя. 8, 2024

АBSTRACT: With increasing incidence and geography, cancer is one of the leading causes death, reduced quality life disability worldwide. Principal progress in development new anticancer therapies, improving efficiency immunotherapeutic tools, personification conventional therapies needs to consider cancer-specific patient-specific programming innate immunity. Intratumoral TAMs their precursors, resident macrophages monocytes, are principal regulators tumor progression therapy resistance. Our review summarizes accumulated evidence for subpopulations number biomarkers, indicating predictive value clinical parameters carcinogenesis resistance, with a focus on solid cancers non-infectious etiology. We present state-of-the-art knowledge about tumor-supporting functions at all stages highlight recently identified by single-cell spatial analytical methods, that discriminate between tumor-promoting tumor-inhibiting TAMs, where both subtypes express combination prototype M1 M2 genes. focuses novel mechanisms involved crosstalk among epigenetic, signaling, transcriptional metabolic pathways TAMs. Particular attention has been given link cell metabolism epigenetic histone lactylation, which can be responsible unlimited protumoral Finally, we explain how interfere currently used therapeutics summarize most advanced data from trials, divide into four categories: inhibition TAM survival differentiation, monocyte/TAM recruitment tumors, functional reprogramming genetic enhancement macrophages.

Язык: Английский

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CAR-macrophage therapy for HER2-overexpressing advanced solid tumors: a phase 1 trial

Nature Medicine, Год журнала: 2025, Номер unknown

Опубликована: Фев. 7, 2025

Язык: Английский

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Targeting macrophages in cancer immunotherapy: Frontiers and challenges

Journal of Advanced Research, Год журнала: 2025, Номер unknown

Опубликована: Янв. 1, 2025

Cancer immunotherapy has emerged as a groundbreaking approach in cancer treatment, primarily realized through the manipulation of immune cells, notably T cell adoption and checkpoint blockade. Nevertheless, cells encounters formidable hurdles. Macrophages, serving pivotal link between innate adaptive immunity, play crucial roles phagocytosis, cytokine secretion, antigen presentation. Consequently, macrophage-targeted therapies have garnered significant attention. We aim to provide most cutting-edge insights future perspectives for therapies, fostering development novel effective treatments. To date, forefront strategies macrophage targeting encompass: altering their plasticity, harnessing CAR-macrophages, phagocytosis checkpoints. Macrophages are characterized by remarkable diversity offering unique therapeutic target. In this context, we critically analyze innovative aimed at transforming macrophages from M2 (tumor-promoting) M1 (tumor-suppressing) phenotype. Furthermore, delve into design principles, developmental progress, advantages CAR-macrophages. Additionally, illuminate challenges encountered checkpoints on propose potential overcome these obstacles.

Язык: Английский

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Targeting conserved TIM3 ⁺ VISTA ⁺ tumor-associated macrophages overcomes resistance to cancer immunotherapy

Science Advances, Год журнала: 2024, Номер 10(29)

Опубликована: Июль 19, 2024

Despite the success of immunotherapy, overcoming immunoresistance in cancer remains challenging. We identified a unique niche tumor-associated macrophages (TAMs), coexpressing T cell immunoglobulin and mucin domain–containing 3 (TIM3) V-domain suppressor activation (VISTA), that dominated human mouse tumors resistant to most currently used immunotherapies. TIM3 + VISTA TAMs were sustained by IL-4–enriching with low (neo)antigenic cell–depleted features. showed an anti-inflammatory protumorigenic phenotype coupled inability sense type I interferon (IFN). This was established cells succumbing immunogenic death (ICD). Dying not only triggered autocrine IFNs but also exposed HMGB1/VISTA engaged TIM3/VISTA on suppress paracrine IFN-responses. Accordingly, blockade synergized paclitaxel, ICD-inducing chemotherapy, repolarize proinflammatory killed via tumor necrosis factor–related apoptosis-inducing ligand (TRAIL) signaling. propose targeting overcome immunoresistant tumors.

Язык: Английский

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Lipid-associated macrophages between aggravation and alleviation of metabolic diseases

Trends in Endocrinology and Metabolism, Год журнала: 2024, Номер 35(11), С. 981 - 995

Опубликована: Май 4, 2024

Lipid-associated macrophages (LAMs) are phagocytic cells with lipid-handling capacity identified in various metabolic derangements. During disease development, they locate to atherosclerotic plaques, adipose tissue (AT) of individuals obesity, liver lesions steatosis and steatohepatitis, the intestinal lamina propria. LAMs can also emerge metabolically demanding microenvironment certain tumors. In this review, we discuss major questions regarding LAM recruitment, differentiation, self-renewal, and, ultimately, their acute chronic functional impact on development diseases. Further studies need clarify whether under which circumstances drive progression or resolution how phenotype be modulated ameliorate disorders.

Язык: Английский

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Crosstalk of pyroptosis and cytokine in the tumor microenvironment: from mechanisms to clinical implication

Molecular Cancer, Год журнала: 2024, Номер 23(1)

Опубликована: Ноя. 30, 2024

In the realm of cancer research, tumor microenvironment (TME) plays a crucial role in initiation and progression, shaped by complex interactions between cells surrounding non-cancerous cells. Cytokines, as essential immunomodulatory agents, are secreted various cellular constituents within TME, including immune cells, cancer-associated fibroblasts, themselves. These cytokines facilitate intricate communication networks that significantly influence initiation, metastasis, suppression. Pyroptosis contributes to TME remodeling promoting release pro-inflammatory sustaining chronic inflammation, impacting processes such escape angiogenesis. However, challenges remain due interplay among cytokines, pyroptosis, along with dual effects pyroptosis on progression therapy-related complications like cytokine syndrome. Unraveling these complexities could strategies balance inflammatory responses while minimizing tissue damage during therapy. This review delves into crosstalk elucidating their contribution metastasis. By synthesizing emerging therapeutic targets innovative technologies concerning this aims provide novel insights enhance treatment outcomes for patients.

Язык: Английский

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Macrophage diversity in human cancers: New insight provided by single-cell resolution and spatial context

Heliyon, Год журнала: 2024, Номер 10(7), С. e28332 - e28332

Опубликована: Март 22, 2024

M1/M2 paradigm of macrophage plasticity has existed for decades. Now it becomes clear that this dichotomy doesn't adequately reflect the diversity phenotypes in tumor microenvironment (TME). Tumor-associated macrophages (TAMs) are a major population innate immune cells TME promotes cell proliferation, angiogenesis and lymphangiogenesis, invasion metastatic niche formation, as well response to anti-tumor therapy. However, fundamental restriction therapeutic TAM targeting is limited knowledge about specific states distinct human cancer types. Here we summarized results most recent studies use advanced technologies (e.g. single-cell RNA sequencing spatial transcriptomics) allowing decipher novel functional subsets TAMs numerous cancers. The transcriptomic profiles these their clinical significance were described. We emphasized characteristics subpopulations – TREM2+, SPP1+, MARCO+, FOLR2+, SIGLEC1+, APOC1+, C1QC+, others, which have been extensively characterized several cancers, associated with prognosis. Spatial transcriptomics defined interactions between other types, especially fibroblasts, tumors. methods also applied identify markers immunotherapy response, expressed by or macrophage-abundant regions. highlighted perspectives techniques utilize single resolution investigating new ligand-receptor effective based on TAM-targeting.

Язык: Английский

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Single-cell sequencing reveals immune features of treatment response to neoadjuvant immunochemotherapy in esophageal squamous cell carcinoma

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Окт. 22, 2024

Neoadjuvant immunochemotherapy (nICT) has dramatically changed the treatment landscape of operable esophageal squamous cell carcinoma (ESCC), but factors influencing tumor response to nICT are not well understood. Here, using single-cell RNA sequencing paired with T receptor sequencing, we profile tissues from ESCC patients accepting and characterize microenvironment context. CXCL13+CD8+ Tex cells, a subset exhausted CD8+ revealed highly infiltrate in pre-treatment tumors show prominent progenitor exhaustion phenotype post-treatment samples responders. We validate cells as predictor improved reveal CXCL13 potentiate anti-PD-1 efficacy vivo. Post-treatment non-responders enriched for notably remarkable TNFRSF4+CD4+ Tregs activated immunosuppressive function significant clone expansion. Several critical markers therapeutic resistance also identified, including LRRC15+ fibroblasts SPP1+ macrophages, which may recruit form an landscape. Overall, our findings unravel immune features distinct treatment, providing rationale optimizing individualized neoadjuvant strategy ESCC. The tumour (ESCC) remain be explored. single TCR on pre- post- identifies presence enrichment marker resistance.

Язык: Английский

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SPP1+ macrophages promote head and neck squamous cell carcinoma progression by secreting TNF-α and IL-1β

Journal of Experimental & Clinical Cancer Research, Год журнала: 2024, Номер 43(1)

Опубликована: Дек. 26, 2024

Язык: Английский

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Engineering CAR‐T Therapeutics for Enhanced Solid Tumor Targeting

Advanced Materials, Год журнала: 2025, Номер unknown

Опубликована: Янв. 2, 2025

Abstract Cancer immunotherapy, specifically Chimeric Antigen Receptor (CAR)‐T cell therapy, represents a significant breakthrough in treating cancers. Despite its success hematological cancers, CAR‐T exhibits limited efficacy solid tumors, which account for more than 90% of all Solid tumors commonly present unique challenges, including antigen heterogeneity and complex tumor microenvironment (TME). To address these, efforts are being made through improvements CAR design the development advanced validation platforms. While is limited, some types, such as neuroblastoma gastrointestinal have shown responsiveness to therapy recent clinical trials. In this review, it first examined both experimental computational strategies, protein engineering coupled with machine learning, developed enhance T specificity. The challenges methods associated delivery vivo reprogramming discussed. It also explored advancements engineered organoid systems, emerging high‐fidelity vitro models that closely mimic human TME serve platform discovery. Collectively, these innovative strategies offer potential revolutionize next generation ultimately paving way effective treatments tumors.

Язык: Английский

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