Unraveling the enigma of tumor-associated macrophages: challenges, innovations, and the path to therapeutic breakthroughs

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: Nov. 14, 2023

Tumor-associated macrophages (TAMs) are integral to the tumor microenvironment (TME), influencing cancer progression significantly. Attracted by cell signals, TAMs exhibit unparalleled adaptability, aligning with dynamic milieu. Their roles span from promoting growth and angiogenesis modulating metastasis. While substantial research has explored fundamentals of TAMs, comprehending their adaptive behavior, leveraging it for novel treatments remains challenging. This review delves into TAM polarization, metabolic shifts, complex orchestration cytokines chemokines determining functions. We highlight complexities TAM-targeted focusing on adaptability potential variability in therapeutic outcomes. Moreover, we discuss synergy integrating TAM-focused strategies established treatments, such as chemotherapy, immunotherapy. Emphasis is laid pioneering methods like reprogramming immunotherapy adoption single-cell technologies precision intervention. synthesis seeks shed light TAMs’ multifaceted cancer, pinpointing prospective pathways transformative enhancing modalities oncology.

Language: Английский

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Dissecting causal links between gut microbiota, inflammatory cytokines, and DLBCL: a Mendelian randomization study

Blood Advances, Journal Year: 2024, Volume and Issue: 8(9), P. 2268 - 2278

Published: March 20, 2024

Causal relationships between gut microbiota, inflammatory cytokines, and diffuse large B-cell lymphoma (DLBCL) remain elusive. In addressing this gap, our Mendelian randomization (MR) study used data from the MiBioGen consortium encompassing 211 microbiota taxa (n = 18 340), genome-wide association meta-analyses of 47 DLBCL cases controls FinnGen (cases, n 1010; controls, 287 137). Through bidirectional MR analyses, we examined causal links mediation including 2-step multivariable (MVMR), to identify potential mediating cytokines. Our findings revealed that 4 were causally associated with DLBCL, conversely, influenced abundance 20 taxa. Specifically, in analysis, both genus Ruminococcaceae UCG-002 (odds ratio [OR], 1.427; 95% confidence interval [CI], 1.011-2.015; P .043) cytokine monokine induced by gamma (MIG) (OR, 1.244; CI, 1.034-1.487; .020) found be an increased risk DLBCL. Additionally, a positive was observed MIG 1.275; 1.069-1.520; .007). Furthermore, MVMR analysis indicated mediated MIG, contributing 14.9% effect (P .005). conclusion, provides evidence supports relationship role played MIG.

Language: Английский

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Single-cell analysis identifies distinct macrophage phenotypes associated with prodisease and proresolving functions in the endometriotic niche

Proceedings of the National Academy of Sciences, Journal Year: 2024, Volume and Issue: 121(38)

Published: Sept. 10, 2024

Endometriosis negatively impacts the health-related quality of life 190 million women worldwide. Novel advances in nonhormonal treatments for this debilitating condition are desperately needed. Macrophages play a vital role pathophysiology endometriosis and represent promising therapeutic target. In current study, we revealed full transcriptomic complexity endometriosis-associated macrophage subpopulations using single-cell analyses preclinical mouse model experimental endometriosis. We have identified two key lesion-resident populations that resemble i) tumor-associated macrophages (characterized by expression Folr2 , Mrc1 Gas6, Ccl8+ ) promoted Col1a1 Tgfb1 human endometrial stromal cells increased angiogenic meshes umbilical vein endothelial cells, ii) scar-associated ( Mmp12, Cd9, Spp1, Trem2 +) exhibited phenotype associated with fibrosis matrix remodeling. also described population proresolving large peritoneal align lipid-associated Apoe, Saa3, Pid1 concomitant altered lipid metabolism cholesterol efflux. Gain function experiments an Apoe mimetic resulted decreased lesion size fibrosis, modification model. Using cross-species analysis datasets, determined concordance subpopulations, identifying similarities differences phenotypes. Ultimately, envisage these findings will inform design use specific macrophage-targeted therapies open broad avenues treatment

Language: Английский

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Single-cell analysis identifies distinct macrophage phenotypes associated with pro-disease and pro-resolving functions in the endometriotic niche

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: March 7, 2024

Abstract Endometriosis negatively impacts the health-related quality of life 190 million women worldwide. Novel advances in non-hormonal treatments for this debilitating condition are desperately needed. Macrophages play a vital role pathophysiology endometriosis and represent promising therapeutic target. In current study, we revealed full transcriptomic complexity endometriosis-associated macrophage subpopulations using single-cell analyses preclinical mouse model experimental endometriosis. We have identified two key lesion-resident populations that resemble i) tumour-associated macrophages (characterized by expression Folr2 , Mrc1 Gas6 Ccl8+ ) promoted Col1a1 Tgfb1 human endometrial stromal cells increased angiogenic meshes umbilical vein endothelial cells, ii) scar-associated ( Mmp12, Cd9, Spp1, Trem2 +) exhibited phenotype associated with fibrosis matrix remodelling. also described population pro-resolving large peritoneal (LpM) align lipid-associated Apoe, Saa3, Pid1 concomitant altered lipid metabolism cholesterol efflux. Gain function experiments an Apoe mimetic resulted decreased lesion size fibrosis, modification model. Using cross-species analysis datasets, determined concordance subpopulations, identifying similarities differences phenotypes. Ultimately, envisage these findings will inform design use specific macrophage-targeted therapies open new avenues treatment

Language: Английский

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Cytokine profiles in patients with newly diagnosed diffuse large B-cell lymphoma: IL-6 and IL-10 levels are associated with adverse clinical features and poor outcomes

Cytokine, Journal Year: 2023, Volume and Issue: 169, P. 156289 - 156289

Published: July 13, 2023

The development of diffuse large B-cell lymphoma (DLBCL), a prevalent subgroup non-Hodgkin (NHL), potentially involves various cytokines. We aimed to determine the correlation between deregulated serum levels cytokines and clinical features investigate their impact on prognosis patients with DLBCL.We conducted retrospective study 77 newly diagnosed DLBCL explore relationships different cytokines, adverse features, poor outcomes. Mann-Whitney U test was used compare cytokine profiles healthy controls. Kaplan-Meier method analyze probability survival, log-rank tests were evaluate differences survival curves. Cox proportional hazards regression model performed univariate multivariate analyses prognostic variables for analyze.Serum interleukin-2 (IL-2), tumor necrosis factor (TNF)-α, IL-6, IL-10, IFN-γ significantly elevated in untreated DLBCL. Serum IL-6 IL-10 higher an International Prognostic Index (IPI) 3-5, bone marrow involvement, LDH ≥ 250 U/L, β2-microglobulin (β2-MG) 2.3 mg/L. Patients B symptoms only had levels, whereas partial response or no treatment as well IL-10. Significant positive correlations observed those β2-MG LDH. 4.5 5.0 pg/mL, combined exhibited shorter progression-free overall survival. Additionally, revealed that pg/mL IPI 3-5 independent factors relapse DLBCL.Pre-treatment might be powerful markers determining predicting

Language: Английский

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Construction of regulatory T cells specific genes predictive models of prostate cancer patients based on machine learning: a computational analysis and in vitro experiments

Discover Oncology, Journal Year: 2025, Volume and Issue: 16(1)

Published: Feb. 13, 2025

Diseases are often caused by multiple factors, regulatory T cells specific genes (RTSGs) have been shown to be associated with cancer, however, their role in prostate cancer (PRAD) has not fully explored. RTSGs PRAD prognosis were identified using Cox regression analysis and LASSO analysis. Furthermore, a prognostic model was constructed based on the 4 RTSGs, its biological function analyzed. We evaluated differences tumor immune microenvironment signature. Finally, cell experiments confirmed of synaptonemal complex protein-2 (SYCP2) cells. The value patients comprehensively analyzed for first time four values. A risk validated an independent external dataset. In patients, this feature is factor significantly correlated clinical information patients. This also related PRAD. Cell that SYCP2 regulates apoptosis cycle progression significantly. Therefore, may become important participating intracellular functional regulation. research provides fundamental theoretical basis improving diagnosis treatment practice.

Language: Английский

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Plasma Cytokine and Chemokine Profiles Predict Efficacy and Toxicity of Anti-CD19 CAR-T Cell Therapy in Large B-cell Lymphoma

Clinical Lymphoma Myeloma & Leukemia, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 1, 2025

Language: Английский

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Angiogenesis-related gene signature for prognostic prediction and immune microenvironment characterization in diffuse large B-cell lymphoma

Clinical and Experimental Medicine, Journal Year: 2025, Volume and Issue: 25(1)

Published: April 8, 2025

Diseases often result from multiple factors, and angiogenesis-related genes (ARGs) have been demonstrated to be associated with cancer. However, their role in diffuse large B-cell lymphoma (DLBCL) has not fully elucidated. ARGs DLBCL prognosis were identified utilizing Cox regression LASSO analyses. A prognostic model was constructed based on 7 ARGs, its biological function analyzed. Differences the tumor immune microenvironment signature evaluated. Finally, cell experiments confirmed differential expression of DLBCL. The value patients comprehensively analyzed for first time, identifying significance. risk these validated an independent external dataset. In patients, this feature factor significantly correlated clinical characteristics. This also significant cells. research provides a fundamental theoretical basis improving diagnosis treatment practice.

Language: Английский

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The cross-talk between B cells and macrophages

International Immunopharmacology, Journal Year: 2024, Volume and Issue: 143, P. 113463 - 113463

Published: Oct. 30, 2024

Language: Английский

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A two-sample Mendelian randomization analysis: causal association between chemokines and pan-carcinoma

Frontiers in Genetics, Journal Year: 2023, Volume and Issue: 14

Published: Nov. 23, 2023

Objective: According to the 2020 data from World Health Organization (WHO), cancers stand as one of foremost contributors global mortality. Revealing novel cancer risk factors and protective is paramount importance in prevention disease occurrence. Studies on relationship between chemokines are ongoing; however, due coordination multiple potential mechanisms, specific causal association remains unclear. Methods: We performed a bidirectional Mendelian randomization analysis explore serum pan-carcinoma. All GWAS catalog IEU Open database. The inverse-variance weighted (IVW) method primarily employed for assessing statistical significance findings. In addition, threshold after hypothesis test (Bonferroni) was 0.0013, evidence considered if p -value < 0.05, but remained greater than Bonferroni’s threshold. Results: results indicate that CCL1 (odds ratio, OR = 1.18), CCL2 (OR 1.04), CCL8 1.36), CCL14 (Colorectal, 1.08, Small intestine, 0.77, Lung, 1.11), CCL15 0.85), CCL18 (Breast, 0.95, Prostate, 0.96), CCL19 (Lung, 0.66, 0.92), CCL20 0.53, Thyroid, 0.76), CCL21 0.62), CCL22 2.05), CCL23 1.31), CCL24 1.06), CCL27 1.49), CCL28 0.74), CXCL5 0.95), CXCL9 3.60), CXCL12 0.87, 0.58), CXCL13 0.93, 1.29), CXCL14 (Colon, 1.40) CXCL17 1.07) cancers. there reverse 0.94) breast cancer. Sensitivity were similar. other four MR Methods consistent with main results, leave-one-out showed not driven by Single nucleotide polymorphism (SNP). Moreover, no heterogeneity pleiotropy our analysis. Conclusion: Based two-sample Analysis method, we found might be upstream pathogenesis. These provide new insights into future use targets treatment. Our also important clues tumor prevention, changes chemokine concentration may recognized features precancerous lesions clinical trials.

Language: Английский

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