Tissue macrophages: origin, heterogenity, biological functions, diseases and therapeutic targets

Signal Transduction and Targeted Therapy, Journal Year: 2025, Volume and Issue: 10(1)

Published: March 7, 2025

Abstract Macrophages are immune cells belonging to the mononuclear phagocyte system. They play crucial roles in defense, surveillance, and homeostasis. This review systematically discusses types of hematopoietic progenitors that give rise macrophages, including primitive progenitors, erythro-myeloid stem cells. These have distinct genetic backgrounds developmental processes. Accordingly, macrophages exhibit complex diverse functions body, phagocytosis clearance cellular debris, antigen presentation, response, regulation inflammation cytokine production, tissue remodeling repair, multi-level regulatory signaling pathways/crosstalk involved homeostasis physiology. Besides, tumor-associated a key component TME, exhibiting both anti-tumor pro-tumor properties. Furthermore, functional status is closely linked development various diseases, cancer, autoimmune disorders, cardiovascular disease, neurodegenerative metabolic conditions, trauma. Targeting has emerged as promising therapeutic strategy these contexts. Clinical trials macrophage-based targeted drugs, immunotherapies, nanoparticle-based therapy were comprehensively summarized. Potential challenges future directions targeting also been discussed. Overall, our highlights significance this versatile cell human health which expected inform research clinical practice.

Language: Английский

---

ALKBH5 acts a tumor-suppressive biomarker and is associated with immunotherapy response in hepatocellular carcinoma

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: Jan. 2, 2025

As immune-checkpoint inhibitors (ICIs) therapy has made great strides in hepatocellular carcinoma (HCC) treatment, improving patient response to this strategy become the main focus of research. Accumulating evidence shown that m6A methylation plays a crucial role tumorigenesis and progression HCC, while precise impact demethylase ALKBH5 on tumor immune microenvironment (TIME) HCC remains poorly defined. The clinical significance TIM3 were evaluated human tissues. biological function was analyzed vitro vivo. molecular subtypes identified based key ALKBH5-regulated methylation-related genes (MRGs). differences survival, features, TIME immunotherapy between these two then evaluated. regulation detected by qPCR, western blotting MeRIP. downregulated associated with worse prognosis. inhibited proliferation migration activities cells subtype high expression MRGs characterized immunosuppression phenotypes ICIs. Moreover, as target ALKBH5. Upregulated level negatively correlated survival HCC. results study suggest is an important regulator progression. exerts its influence targeting This work provides new insight into correlation modification ICI response, which may help provide therapeutic benefits patients.

Language: Английский

---

Tumor-Associated Macrophages as Major Immunosuppressive Cells in the Tumor Microenvironment

Cancers, Journal Year: 2024, Volume and Issue: 16(19), P. 3410 - 3410

Published: Oct. 8, 2024

Within the tumor microenvironment, myeloid cells constitute a dynamic immune population characterized by heterogeneous phenotype and diverse functional activities. In this review, we consider recent literature shedding light on increasingly complex biology of M2-like immunosuppressive tumor-associated macrophages (TAMs), including their contribution to cell invasion metastasis, stromal remodeling (fibrosis matrix degradation), suppressive functions, in microenvironment (TME). This review also delves into intricate signaling mechanisms underlying polarization macrophage phenotypes, plasticity. We development promising therapeutic approaches target these populations cancers. The expanding knowledge distinct subsets TAMs, contributions tumorigenesis has sparked significant interest among researchers regarding potential TAM depletion or phenotypic modulation.

Language: Английский

---

Trial watch: anticancer vaccination with dendritic cells

OncoImmunology, Journal Year: 2024, Volume and Issue: 13(1)

Published: Oct. 9, 2024

Dendritic cells (DCs) are critical players at the intersection of innate and adaptive immunity, making them ideal candidates for anticancer vaccine development. DC-based immunotherapies typically involve isolating patient-derived DCs, pulsing with tumor-associated antigens (TAAs) or tumor-specific (TSAs), utilizing maturation cocktails to ensure their effective activation. These matured DCs then reinfused elicit T-cell responses. While this approach has demonstrated ability generate potent immune responses, its clinical efficacy been limited due immunosuppressive tumor microenvironment. Recent efforts have focused on enhancing immunogenicity vaccines, particularly through combination therapies T cell-targeting immunotherapies. This Trial Watch summarizes recent advances in cancer treatments, including development new preclinical strategies, discusses future potential vaccines evolving landscape immuno-oncology.

Language: Английский

---

Immunosensitivity cuts across mismatch repair status in colorectal cancer

Cancer Cell, Journal Year: 2025, Volume and Issue: 43(2), P. 175 - 177

Published: Feb. 1, 2025

Language: Английский

---

Soluble TIM-3, likely produced by myeloid cells, predicts resistance to immune checkpoint inhibitors in metastatic clear cell renal cell carcinoma

Journal of Experimental & Clinical Cancer Research, Journal Year: 2025, Volume and Issue: 44(1)

Published: Feb. 14, 2025

Abstract Background Immunotherapies targeting PD-1 and CTLA-4 are key components of the treatment metastatic clear cell renal carcinoma (mccRCC). However, they have distinct safety profiles resistance to can occur. We assess soluble TIM-3 (sTIM-3) in plasma mccRCC patients as a potential theranostic biomarker, well its source biological significance. Methods analyzed association between sTIM-3 overall survival (OS), tumor response, common clinical factors two cohorts treated with anti-PD-1 (nivolumab, n = 27), or + anti-CTLA-4 (nivolumab ipilimumab – N I, 124). The origin role studied on blood samples, using multiplex immunohistochemistry flow cytometry, analyses publicly available single-cell transcriptomic (scRNAseq) mass cytometry data. Results is significantly elevated treatment-naive mccRCC. It shows associations vs anti-CTLA-4: under nivolumab monotherapy, sTIM-3-high reduced compared sTIM-3-low patients, while similar probabilities I. independent from other factors. Myeloid immune cells appear prominent sTIM-3, which may indicate their dysfunctional antitumor response. Conclusions appears be promising biomarker for optimizing strategies ccRCC therapeutic target, linked myeloid compartment. Future investigations warranted antiangiogenic therapies.

Language: Английский

---

The diversity of CD8+ T cell dysfunction in cancer and viral infection

Nature reviews. Immunology, Journal Year: 2025, Volume and Issue: unknown

Published: April 11, 2025

Language: Английский

---

Macrophages suppress CD8 + T cell cytotoxic function in triple negative breast cancer via VISTA

British Journal of Cancer, Journal Year: 2025, Volume and Issue: unknown

Published: May 2, 2025

Language: Английский

---

FEM1B enhances TRAIL‐induced apoptosis in T lymphocytes and monocytes

FEBS Open Bio, Journal Year: 2025, Volume and Issue: unknown

Published: May 20, 2025

FEM1B is recognized for its significant pro‐apoptotic function in colorectal cancer; however, influence and mechanisms regarding apoptosis immune cells remain inadequately elucidated. In this study, we demonstrated that enhances TRAIL‐induced Molt‐4, Jurkat, THP‐1, U937 cell lines. Notably, the knockdown of transfected resulted a reversal observed increase apoptosis. Our findings indicate activates caspase‐3 caspase‐8, but not caspase‐9, response to TRAIL stimulation, suggesting involvement extrinsic caspase‐dependent apoptotic pathway. Furthermore, found interacted with TRAF2 downregulates expression Molt‐4 Jurkat cells, thereby diminishing TRAF2's inhibitory effect on caspase‐8. THP‐1 was upregulate TRAIL‐R2, promoting Knockout studies murine models further corroborated facilitates These results demonstrate T lymphocytes monocytes through mechanism involving or receptors.

Language: Английский

---

Roles of macrophages and monocytes in resistance to immunotherapy in breast cancers

Postgraduate Medical Journal, Journal Year: 2025, Volume and Issue: unknown

Published: May 6, 2025

Abstract Background Immunotherapy is increasingly integral to breast cancer treatment, yet a subset develops resistance, partly mediated by macrophages and monocytes in the tumor immune microenvironment. While play essential roles phagocytosis pathogen clearance, their dual role cancer—acting as both barriers therapy potential therapeutic targets—complicates treatment efficacy. Strategy Tumor-associated macrophages, polarized tumor-derived signals, promote progression metastasis. Monocytes, subdivided into CD14+CD16− CD14+CD16+ subsets, exhibit distinct functional profiles cytokine secretion, antigen presentation, migration. Modulating monocyte dynamics functionality may enhance immunotherapy responsiveness. Conclusion A multimodal strategy targeting monocytes, complementary immunotherapies offers promising avenues overcome resistance. Further research heterogeneity regulatory mechanisms of these cells critical for developing optimized, safe immunotherapeutic protocols. This review underscores necessity combination improve outcomes cancer.

Language: Английский

---