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

Signal Transduction and Targeted Therapy, Год журнала: 2025, Номер 10(1)

Опубликована: Март 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.

Язык: Английский

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FASN-mediated fatty acid biosynthesis remodels immune environment in Clonorchis sinensis infection-related intrahepatic cholangiocarcinoma

Journal of Hepatology, Год журнала: 2024, Номер 81(2), С. 265 - 277

Опубликована: Март 19, 2024

Язык: Английский

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Enhanced antitumour immunity following neoadjuvant chemoradiotherapy mediates a favourable prognosis in women with resected pancreatic cancer

Gut, Год журнала: 2023, Номер 73(2), С. 311 - 324

Опубликована: Сен. 14, 2023

Background This study investigates sex disparities in clinical outcomes and tumour immune profiles patients with pancreatic ductal adenocarcinoma (PDAC) who underwent upfront resection or preceded by gemcitabine-based neoadjuvant chemoradiotherapy (nCRT). Methods Patients originated from the PREOPANC randomised controlled trial. Upfront surgery was performed 82 patients, 66 received nCRT before resection. The impact of on overall survival (OS) investigated using Cox proportional hazards models. immunological landscape within microenvironment (TME) mapped transcriptomic spatial proteomic profiling. Results 5-year OS rate differed between sexes following nCRT, 43% for women compared 22% men. In multivariate analysis, female a favourable independent prognostic factor only group (HR 0.19; 95% CI 0.07 to 0.52). Multivariate heterogeneous treatment effects analysis revealed significant interaction treatment, implying increased efficacy among resected PDAC. TME contained fewer protumoural CD163+MRC1+M2 macrophages than that men after as indicated validated Conclusion PDAC tumours are more sensitive resulting longer may be due enhanced immunity impeding infiltration protumoral M2 into TME. Our findings highlight importance considering mitigating immunosuppressive macrophage polarisation personalised treatment.

Язык: Английский

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Tumor-associated macrophages affect the treatment of lung cancer

Heliyon, Год журнала: 2024, Номер 10(7), С. e29332 - e29332

Опубликована: Апрель 1, 2024

As one of the most common malignant tumors in world, lung cancer has limited benefits for patients despite its diverse treatment methods due to factors such as personalized medicine targeting histological type, immune checkpoint expression, and driver gene mutations. The high mortality rate is partly immune-suppressive which limits effectiveness anti-cancer drugs induces tumor cell resistance. currently widely recognized TAM phenotypes include anti-tumor M1 pro-tumor M2 phenotypes. macrophages promote formation an microenvironment hinder infiltration, thereby inhibiting activation system aiding cells resisting treatment. Analyzing relationship between different TME can help us better understand impact TAMs on confirm feasibility targeted therapy. Targeting reduce M2/M1 ratio reverse improve clinical efficacy conventional potentially open up more efficient combination strategies, maximizing benefit patients.

Язык: Английский

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Prognostic value of CD163+ macrophages in solid tumor malignancies: A scoping review

Immunology Letters, Год журнала: 2025, Номер unknown, С. 106970 - 106970

Опубликована: Янв. 1, 2025

Tumor-associated macrophages (TAMs) play crucial roles in development and progression of malignant diseases. Notably, CD163

Язык: Английский

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SPI1⁺CD68⁺macrophages as a biomarker for gastric cancer metastasis: a rationale for combined antiangiogenic and immunotherapy strategies

Journal for ImmunoTherapy of Cancer, Год журнала: 2024, Номер 12(10), С. e009983 - e009983

Опубликована: Окт. 1, 2024

Tumor-associated macrophages (TAMs) have been demonstrated to be associated with tumor progression. However, the different subpopulations of TAMs and their roles in gastric cancer (GC) remain poorly understood. This study aims assess effects Spi-1 proto-oncogene (SPI1)

Язык: Английский

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PI3Kγ inhibition combined with DNA vaccination unleashes a B-cell-dependent antitumor immunity that hampers pancreatic cancer

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

Опубликована: Июнь 1, 2024

Abstract Phosphoinositide-3-kinase γ (PI3Kγ) plays a critical role in pancreatic ductal adenocarcinoma (PDA) by driving the recruitment of myeloid-derived suppressor cells (MDSC) into tumor tissues, leading to growth and metastasis. MDSC also impair efficacy immunotherapy. In this study we verify hypothesis that targeting, via PI3Kγ inhibition, synergizes with α-enolase (ENO1) DNA vaccination counteracting growth. Mice received ENO1 followed inhibition had significantly smaller tumors compared those treated alone or control group, correlated i) increased circulating anti-ENO1 specific IgG IFNγ secretion T cells, ii) infiltration CD8 + M1-like macrophages, as well up-modulation cell activation related transcripts, iii) decreased Treg FoxP3 endothelial pericytes, down-modulation stromal compartment exhaustion gene transcription, iv) reduction mature neo-formed vessels, v) follicular helper vi) “antigen spreading”, many other tumor-associated antigens were recognized IgG2c “cytotoxic” antibodies. PDA mouse models genetically devoid showed an survival pattern transcripts area similar pharmacologically-inhibited PI3Kγ-proficient mice. Notably, was abrogated inhibition-treated mice which B depleted. These data highlight novel cell-dependent immunity, suggesting depletion strengthens anti-tumor response elicited vaccine.

Язык: Английский

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Imaging of tumor-associated macrophage dynamics during immunotherapy using a CD163-specific nanobody-based immunotracer

Proceedings of the National Academy of Sciences, Год журнала: 2024, Номер 121(52)

Опубликована: Дек. 18, 2024

Immunotherapies have emerged as an effective treatment option for immune-related diseases, such cancer and inflammatory diseases. However, variations in patient responsiveness limit the broad applicability success of these immunotherapies. Noninvasive whole-body imaging immune status individual patients during immunotherapy could enable prediction monitoring patient’s response, resulting more personalized treatments. In this study, we developed a nanobody-based immunotracer targeting CD163, receptor specifically expressed on macrophages. This anti-CD163 bound to human mouse CD163 with high affinity specificity without competing ligand binding. Furthermore, tracer showed no unwanted cell activation was nonimmunogenic. Upon radiolabeling immunotracer, specific + macrophages using micro-single-photon emission computerized tomography/computed tomography or micro-positron tomography/CT performed. The able stratify responders from nonresponders (NR) by visualizing differences intratumoral TAM distribution Lewis lung carcinoma-ovalbumin tumor-bearing mice receiving anti-programmed death protein-1 (PD-1)/CSF1R combination treatment. Immunotherapy-responding homogeneous PET signal middle tumor, while TAMs were located at tumor periphery NR. As such, visualization microenvironment allow follow-up therapy response. Altogether, study describes macrophages, that allows same-day cells microenvironment, providing good basis responses patients.

Язык: Английский

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Tumour-associated macrophages: versatile players in the tumour microenvironment

Frontiers in Cell and Developmental Biology, Год журнала: 2023, Номер 11

Опубликована: Окт. 26, 2023

Tumour-Associated Macrophages (TAMs) are one of the pivotal components tumour microenvironment. Their roles in cancer immunity complicated, both pro-tumour and anti-cancer activities reported, including not only angiogenesis, extracellular matrix remodeling, immunosuppression, drug resistance but also phagocytosis regression. Interestingly, TAMs highly dynamic versatile solid tumours. They show or activities, interplay between microenvironment stem cells under specific conditions. In addition to classic M1/M2 phenotypes, a number novel dedifferentiation phenomena discovered due advanced single-cell technology, e.g., macrophage-myofibroblast transition (MMT) macrophage-neuron (MNT). More importantly, emerging information demonstrated potential on immunotherapy, suggesting by therapeutic efficiency checkpoint inhibitors chimeric antigen receptor engineered based macrophages. Here, we summarized latest discoveries from basic translational research discussed their clinical relevance for cancers.

Язык: Английский

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Exploring the Prognostic Role of Trop-2, CD47, and CD163 Expression Levels on Survival Outcomes in Patients with Triple-Negative Breast Cancer

Diagnostics, Год журнала: 2025, Номер 15(2), С. 232 - 232

Опубликована: Янв. 20, 2025

Background: This study evaluated the prognostic impact of Trop-2, CD47, and CD163 expression on clinical outcomes in triple-negative breast cancer (TNBC) investigated their interactions with tumor progression. Methods: A retrospective cohort 92 patients TNBC was analyzed. The scores for were categorized as negative/low (0–3 points) or high (4–6 points). primary endpoint overall survival (OS). Results: median age 50 years old. High Trop-2 observed 55.4% significantly associated advanced disease stage (p < 0.001). CD47 (44.6%) correlated = 0.044), whereas (45.7%) 0.021), absence comorbidities 0.022), lower pT 0.023). Moderate positive correlations found between 0.037), 0.001), respectively. Kaplan–Meier analysis revealed that low exhibited prolonged OS 0.021) progression-free (PFS) 0.026) compared to those expression. Univariate multivariate analyses significant associations PFS lymphovascular invasion, BRCA status. Conclusions: is a factor worse outcomes. Although showed trends poorer prognosis, significance not confirmed. These findings offer promising prospects future studies combined antibody–drug conjugates (ADCs), they may present opportunities address multiple resistance mechanisms management enhance

Язык: Английский

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