Deep learning system for malignancy risk prediction in cystic renal lesions: a multicenter study.

OBJECTIVES: To develop an interactive, non-invasive artificial intelligence (AI) system for malignancy risk prediction in cystic renal lesions (CRLs). METHODS: In this retrospective, multicenter diagnostic study, we evaluated 715 patients. An interactive geodesic-based 3D segmentation model was created for CRLs segmentation. A CRLs classification model was developed using spatial encoder temporal decoder (SETD) architecture. The classification model combines a 3D-ResNet50 network for extracting spatial features and a gated recurrent unit (GRU) network for decoding temporal features from multi-phase CT images. We assessed the segmentation model using sensitivity (SEN), specificity (SPE), intersection over union (IOU), and dice similarity (Dice) metrics. The classification model's performance was evaluated using the area under the receiver operator characteristic curve (AUC), accuracy score (ACC), and decision curve analysis (DCA). RESULTS: From 2012 to 2023, we included 477 CRLs (median age, 57 [IQR: 48-65]; 173 men) in the training cohort, 226 CRLs (median age, 60 [IQR: 52-69]; 77 men) in the validation cohort, and 239 CRLs (median age, 59 [IQR: 53-69]; 95 men) in the testing cohort (external validation cohort 1, cohort 2, and cohort 3). The segmentation model and SETD classifier exhibited excellent performance in both validation (AUC = 0.973, ACC = 0.916, Dice = 0.847, IOU = 0.743, SEN = 0.840, SPE = 1.000) and testing datasets (AUC = 0.998, ACC = 0.988, Dice = 0.861, IOU = 0.762, SEN = 0.876, SPE = 1.000). CONCLUSION: The AI system demonstrated excellent benign-malignant discriminatory ability across both validation and testing datasets and illustrated improved clinical decision-making utility. CRITICAL RELEVANCE STATEMENT: In this era when incidental CRLs are prevalent, this interactive, non-invasive AI system will facilitate accurate diagnosis of CRLs, reducing excessive follow-up and overtreatment. KEY POINTS: The rising prevalence of CRLs necessitates better malignancy prediction strategies. The AI system demonstrated excellent diagnostic performance in identifying malignant CRL. The AI system illustrated improved clinical decision-making utility.

Unbiased metastatic niche-labeling identifies estrogen receptor-positive macrophages as a barrier of T cell infiltration during bone colonization.

Microenvironment niches determine cellular fates of metastatic cancer cells. However, robust and unbiased approaches to identify niche components and their molecular profiles are lacking. We established Sortase A-Based Microenvironment Niche Tagging (SAMENT), which selectively labels cells encountered by cancer cells during metastatic colonization. SAMENT was applied to multiple cancer models colonizing the same organ and the same cancer to different organs. Common metastatic niche features include macrophage enrichment and T cell depletion. Macrophage niches are phenotypically diverse between different organs. In bone, macrophages express the estrogen receptor alpha (ERα) and exhibit active ERα signaling in male and female hosts. Conditional knockout of Esr1 in macrophages significantly retarded bone colonization by allowing T cell infiltration. ERα expression was also discovered in human bone metastases of both genders. Collectively, we identified a unique population of ERα+ macrophages in the metastatic niche and functionally tied ERα signaling in macrophages to T cell exclusion during metastatic colonization. HIGHLIGHTS: SAMENT is a robust metastatic niche-labeling approach amenable to single-cell omics.Metastatic niches are typically enriched with macrophages and depleted of T cells.Direct interaction with cancer cells induces ERα expression in niche macrophages. Knockout of Esr1 in macrophages allows T cell infiltration and retards bone colonization.

Integrative spatial omics reveals distinct tumor-promoting multicellular niches and immunosuppressive mechanisms in African American and European American patients with TNBC.

Racial disparities in triple-negative breast cancer (TNBC) outcomes have been reported. However, the biological mechanisms underlying these disparities remain unclear. We integrated imaging mass cytometry and spatial transcriptomics, to characterize the tumor microenvironment (TME) of African American (AA) and European American (EA) patients with TNBC. The TME in AA patients was characterized by interactions between endothelial cells, macrophages, and mesenchymal-like cells, which were associated with poor patient survival. In contrast, the EA TNBC-associated niche is enriched in T-cells and neutrophils suggestive of an exhaustion and suppression of otherwise active T cell responses. Ligand-receptor and pathway analyses of race-associated niches found AA TNBC to be immune cold and hence immunotherapy resistant tumors, and EA TNBC as inflamed tumors that evolved a distinctive immunosuppressive mechanism. Our study revealed the presence of racially distinct tumor-promoting and immunosuppressive microenvironments in AA and EA patients with TNBC, which may explain the poor clinical outcomes.

Simple and sensitive sandwich-like electrochemical immunosensing strategy for D-dimer based on cyclodextrin-carbon nanotube and nanogold-ferrocene.

D-dimer is a very important biomarker about sepsis, pulmonary thromboembolism and atherosclerosis, thus designing effective and sensitive method for its detection is of great significance. Herein, by synthesizing ß-cyclodextrin-carbon nanotube nanohybrid (CNTs-CD) as the carrier to assemble the initial antibody (Ab1) of D-dimer, immobilizing secondary antibody (Ab2) and sulfydryl ferrocene (Fc) on the nanogold (Au) particles surface as the signaling amplifier (Ab2-Au-Fc), a low cost, simple, sensitive and effective sandwich-like electrochemical immunosensing (SEI) platform of D-dimer was proposed in this work for the first time. Briefly, CNTs shows large specific area and superior electroconductivity, and CD provides high host guest recognition ability that could bound with Ab1; meanwhile, the Fc probe offers stable current response which are proportionable positively to the level of D-dimer. Under the best conditions, the designed SEI platform exhibits prominent analytical performances for D-dimer: low detection limit of 3.0 ng mL-1 and large linearity of 10.0-800.0 ng mL-1. In addition, the selectivity, stability and reproducibility as well as real applications of the proposed SEI assay were evaluated and the obtained results are satisfactory.

Pseudomonas aeruginosa Lipid A Structural Variants Induce Altered Immune Responses.

Pseudomonas aeruginosa causes chronic lung infection in cystic fibrosis (CF), resulting in structural lung damage and progressive pulmonary decline. P. aeruginosa in the CF lung undergoes numerous changes, adapting to host-specific airway pressures while establishing chronic infection. P. aeruginosa undergoes lipid A structural modification during CF chronic infection, not seen in any other disease state. Lipid A, the membrane anchor of lipopolysaccharide (i.e., endotoxin), comprises the majority of the outer membrane of Gram-negative bacteria and is a potent toll-like receptor (TLR)4 agonist. The structure of P. aeruginosa lipid A is intimately linked with its recognition by TLR4, and subsequent immune response. Prior work has identified P. aeruginosa strains with altered lipid A structures that arise during chronic CF lung infection; however, the impact of P. aeruginosa lipid A structure on airway disease has not been investigated. Here, we show that P. aeruginosa lipid A lacks PagL-mediated deacylation during human airway infection using a direct-from-sample mass spectrometry approach on human bronchoalveolar lavage fluid. This structure triggers increased pro-inflammatory cytokine production by primary human macrophages. Furthermore, alterations in lipid A 2-hydroxylation impact cytokine response in a site-specific manner, independent of CFTR function. Interestingly, there is a CF-specific reduction in IL-8 secretion within the epithelial-cell compartment that only occurs in CF bronchial epithelial cells when infected with CF-adapted P. aeruginosa that lack PagL-mediated lipid A deacylation. Taken together, we show that P. aeruginosa alters its lipid A structure during acute lung infection and that this lipid A structure induces stronger signaling through TLR4.

Gas-Liquid Interface Route to Hybrid Copper Bromine Perovskite Single-Crystal Membrane with Dielectric Transitions and Ferromagnetic Exchanges.

Single-crystal membranes (SCMs) show great promise in the fields of sensors, light-emitting diodes, and photodetection. However, the growth of a large-area single-crystal membranes is challenging. We report a new organic-inorganic SCMs [HCMA]2CuBr4 (HCMA = cyclohexanemethylamine) crystallized at the gas-liquid interface. It also has low-temperature ferromagnetic order, high-temperature dielectric anomalies, and narrow band gap indirect semiconductor properties. Specifically, the reversible phase transition of the compound occurs at 350/341 K on cooling/heating and exhibits dielectric anomalies and stable switching performance near the phase transition temperature. The ferromagnetic exchange interaction in the inorganic octahedra and the organic layer enables ferromagnetic ordering at low-temperature 10 K. Finally, the single crystal exhibits an indirect semiconducting property with a narrow band gap of 0.99 eV. Such rich multichannel physical properties make it a potential application in photodetection, information storage and sensors.

Added value of DCER-features to clinicopathologic model for predicting metachronous metastases in rectal cancer patients.

RATIONALE AND OBJECTIVES: The study aimed to investigate whether dynamic contrast-enhanced MRI parameters and preoperative radiological features (DCER-Features) add value to the clinicopathologic model for predicting metachronous metastases in rectal cancer patients. MATERIALS AND METHODS: From January 2014 to December 2020, 859 patients in the PACS system were retrospectively screened. Of the initial 722 patients with surgically confirmed rectal cancer and no synchronous metastases, 579 patients were excluded for various reasons such as lack of clinicopathological or radiological information. 143 patients were finally included in this study. And 73 Patients of them developed metachronous metastasis within five years. After stepwise multiple regression analyses, we constructed three distinct models. Model 1 was developed solely based on clinicopathological factors, and model 2 incorporated clinicopathological characteristics along with DCE-MRI parameters. Finally, model 3 was built on all available factors, including clinicopathological characteristics, DCE-MRI parameters, and radiological features based on rectal magnetic resonance imaging. The radiological features assessed in this study encompass tumor imaging staging, location, and circumferential resection margin (CRM) for primary tumors, as well as the number of visible lymph nodes and suspected metastatic lymph nodes. Receiver operating characteristic (ROC) and decision curve analysis (DCA) were conducted to evaluate whether the diagnostic efficiency was improved. RESULTS: The performance of model 3 (including clinicopathologic characteristics and DCER-Features) was the best (AUC: 0.856, 95% CI 0.778-0.886), whereas it was 0.796 (95% CI 0.720-0.828) for model 2 and 0.709 (95% CI 0.612-0.778) for model 1 (DeLong test: model 1 vs model 2, p = 0.004; model 2 vs model 3, p = 0.037; model 1 vs model 3, p < 0.001). The decision curves indicated that the net benefit of model 3 was higher than the other two models at each referral threshold. The calibration plot of the three models revealed an excellent predictive accuracy. CONCLUSION: This study suggests that DCER-Features have added value for the clinicopathological model to predict metachronous metastasis in patients with rectal cancers.

Investigating the causal relationship and potential shared diagnostic genes between primary biliary cholangitis and systemic lupus erythematosus using bidirectional Mendelian randomization and transcriptomic analyses.

Background: The co-occurrence of primary biliary cholangitis (PBC) and systemic lupus erythematosus (SLE) has been consistently reported in observational studies. Nevertheless, the underlying causal correlation between these two conditions still needs to be established. Methods: We performed a bidirectional two-sample Mendelian randomization (MR) study to assess their causal association. Five MR analysis methods were utilized for causal inference, with inverse-variance weighted (IVW) selected as the primary method. The Mendelian Randomization Pleiotropy RESidual Sum and Outlier (MR-PRESSO) and the IVW Radial method were applied to exclude outlying SNPs. To assess the robustness of the MR results, five sensitivity analyses were carried out. Multivariable MR (MVMR) analysis was also employed to evaluate the effect of possible confounders. In addition, we integrated transcriptomic data from PBC and SLE, employing Weighted Gene Co-expression Network Analysis (WGCNA) to explore shared genes between the two diseases. Then, we used Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment methods to perform on the shared genes. The Least Absolute Shrinkage and Selection Operator (LASSO) regression algorithm was utilized to identify potential shared diagnostic genes. Finally, we verified the potential shared diagnostic genes in peripheral blood mononuclear cells (PBMCs)-specific cell populations of SLE patients by single-cell analysis. Results: Our MR study provided evidence that PBC had a causal relationship with SLE (IVW, OR: 1.347, 95% CI: 1.276 - 1.422, P < 0.001) after removing outliers (MR-PRESSO, rs35464393, rs3771317; IVW Radial, rs11065987, rs12924729, rs3745516). Conversely, SLE also had a causal association with PBC (IVW, OR: 1.225, 95% CI: 1.141 - 1.315, P < 0.001) after outlier correction (MR-PRESSO, rs11065987, rs3763295, rs7774434; IVW Radial, rs2297067). Sensitivity analyses confirmed the robustness of the MR findings. MVMR analysis indicated that body mass index (BMI), smoking and drinking were not confounding factors. Moreover, bioinformatic analysis identified PARP9, ABCA1, CEACAM1, and DDX60L as promising diagnostic biomarkers for PBC and SLE. These four genes are highly expressed in CD14+ monocytes in PBMCs of SLE patients and potentially associated with innate immune responses and immune activation. Conclusion: Our study confirmed the bidirectional causal relationship between PBC and SLE and identified PARP9, ABCA1, CEACAM1, and DDX60L genes as the most potentially shared diagnostic genes between the two diseases, providing insights for the exploration of the underlying mechanisms of these disorders.

Seeding Activity of Skin Misfolded Tau as a Biomarker for Tauopathies.

Background: Tauopathies are a group of age-related neurodegenerative diseases characterized by the accumulation of pathologically phosphorylated tau protein in the brain, leading to prion-like propagation and aggregation. They include Alzheimer's disease (AD), progressive supranuclear palsy (PSP), corticobasal degeneration (CBD), and Pick's disease (PiD). Currently, reliable diagnostic biomarkers that directly reflect the capability of propagation and spreading of misfolded tau aggregates in peripheral tissues and body fluids are lacking. Methods: We utilized the seed-amplification assay (SAA) employing ultrasensitive real-time quaking-induced conversion (RT-QuIC) to assess the prion-like seeding activity of pathological tau in the skin of cadavers with neuropathologically confirmed tauopathies, including AD, PSP, CBD, and PiD, compared to normal controls. Results: We found that the skin prion-SAA demonstrated a significantly higher sensitivity (75-80%) and specificity (95-100%) for detecting tauopathy, depending on the tau substrates used. Moreover, increased tau-seeding activity was also observed in biopsy skin samples from living AD and PSP patients examined. Analysis of the end products of skin-tau SAA confirmed that the increased seeding activity was accompanied by the formation of tau aggregates with different physicochemical properties related to two different tau substrates used. Conclusions: Overall, our study provides proof-of-concept that the skin tau-SAA can differentiate tauopathies from normal controls, suggesting that the seeding activity of misfolded tau in the skin could serve as a diagnostic biomarker for tauopathies.

[Multi-Voiced Narrative of Home-Based Palliative Care:Report of One Case].

Terminally ill patients face multiple difficulties in home care.Home-based palliative care adhering to the concept of whole-person,whole-family,whole-team,and whole-course care is able to meet the needs of terminally ill patients and their families.In this paper,we reported the care history and home-based palliative care process of a patient with end-stage breast tumor and summarized the experience,aiming to provide reference for the future work of home-based palliative care.

Redox proteomics of PANC-1 cells reveals the significance of HIF-1 signaling protein oxidation in pancreatic ductal adenocarcinoma pathogenesis.

BACKGROUND: Protein cysteine oxidation is substantially involved in various biological and pathogenic processes, but its implications in pancreatic cancer development remains poorly understood. METHODS AND RESULTS: In this study, we performed a global characterization of protein oxidation targets in PDAC cells through iodoTMT-based quantitative proteomics, which identified over 4300 oxidized cysteine sites in more than 2100 proteins in HPDE6c7 and PANC-1 cells. Among them, 1715 cysteine residues were shown to be differentially oxidized between HPDE6c7 and PANC-1 cells. Also, charged amino acids including aspartate, glutamate and lysine were significantly overrepresented in flanking sequences of oxidized cysteines. Differentially oxidized proteins in PANC-1 cells were enriched in multiple cancer-related biological processes and signaling pathways. Specifically, the HIF-1 signaling proteins exhibited significant oxidation alterations in PANC-1 cells, and the reduced PHD2 oxidation in human PDAC tissues was correlated with lower survival time in pancreatic cancer patients. CONCLUSION: These investigations provided new insights into protein oxidation-regulated signaling and biological processes during PDAC pathogenesis, which might be further explored for pancreatic cancer diagnosis and treatment.

Halogen-Regulated Tc and X-ray Radiation Detection in 2D Hybrid Perovskite Ferroelastic Semiconductor.

Organic-inorganic hybrid perovskites (OIHPs) have received particular attention due to their characteristic structural tunability and flexibility. These features make OIHPs behave with excellent modifications on macroscopic properties, such as ferroicity or semiconductor performances, etc. Herein, we report two 2D hybrid stibium-based halide perovskite (C3H7N)3Sb2X9 (X = Br, 1; Cl, 2) ferroelastic semiconductor possessing dual switching properties of dielectric and second harmonic generation (SHG). Notably, these two hybrids exhibit halogen-regulated ferroelasticity and semiconductor properties. There is a significant difference in Curie temperature (Tc) and X-ray radiation detection sensitivity (S), i.e., the ΔTc and ΔS are 38 K and 87 µC Gyair-1 cm-2, respectively. Meanwhile, crystals 1 and 2 do not show dark current drift in cyclic measurements of different radiation doses with stable switching ratios of 30 and 10, separately. Meanwhile, these results were proven by scientific experimental results and density functional theory (DFT) calculations. Our work presents a facile and practical method to regulate macroproperties on the molecular level, providing a new vision to develop hybrid perovskite ferroic-photoelectric materials.

REGγ Mitigates Radiation-Induced Enteritis by Preserving Mucin Secretion and Sustaining Microbiome Homeostasis.

Radiation-induced enteritis, a significant concern in abdominal radiation therapy, is associated closely with gut microbiota dysbiosis. The mucus layer plays a pivotal role in preventing the translocation of commensal and pathogenic microbes. Although significant expression of REGγ in intestinal epithelial cells is well established, its role in modulating the mucus layer and gut microbiota remains unknown. The current study revealed notable changes in gut microorganisms and metabolites in irradiated mice lacking REGγ, as compared to wild-type mice. Concomitant with gut microbiota dysbiosis, REGγ deficiency facilitated the infiltration of neutrophils and macrophages, thereby exacerbating intestinal inflammation after irradiation. Furthermore, fluorescence in situ hybridization assays unveiled an augmented proximity of bacteria to intestinal epithelial cells in REGγ knockout mice after irradiation. Mechanistically, deficiency of REGγ led to diminished goblet cell populations and reduced expression of key goblet cell markers, Muc2 and Tff3, observed in both murine models, minigut organoid systems and human intestinal goblet cells, indicating the intrinsic role of REGγ within goblet cells. Interestingly, although administration of broad-spectrum antibiotics did not alter the goblet cell numbers or mucin 2 (MUC2) secretion, it effectively attenuated inflammation levels in the ileum of irradiated REGγ absent mice, bringing them down to the wild-type levels. Collectively, these findings highlight the contribution of REGγ in counteracting radiation-triggered microbial imbalances and cell-autonomous regulation of mucin secretion.

Glaucoma drainage device implantation and cyclophotocoagulation in the management of refractory glaucoma after Descemet-stripping automated endothelial keratoplasty.

AIM: To compare the surgical outcomes of glaucoma drainage device implantation (GDI) and trans-scleral neodymium:YAG cyclophotocoagulation (CPC) in the management of refractory glaucoma after Descemet-stripping automated endothelial keratoplasty (DSAEK). METHODS: This retrospective study on observational case series enrolled 29 patients who underwent DSAEK and posterior anti-glaucoma surgery (15 with GDI and 14 with CPC). The main outcome measures were intraocular pressure (IOP), glaucoma surgery success rate (defined as IOP of 6-21 mm Hg without additional anti-glaucoma operation), number of glaucoma medications, endothelial graft status, and best-corrected visual acuity (BCVA). RESULTS: The mean follow-up time was 34.1 and 21.0mo for DSAEK or glaucoma surgeries, both for the GDI and CPC groups. Both groups showed significant IOP reduction after glaucoma surgery. The GDI group presented a significantly higher success rate in IOP control than the CPC group (60% vs 21.4%, P=0.03). Both procedures significantly decreased the number of glaucoma medications (P=0.03). Forty percent and 57% of cases in the GDI and the CPC group, respectively, experienced endothelial graft failure during follow-up (P=0.36). Significantly worse BCVA after surgery was observed in the CPC group but not in the GDI group. CONCLUSION: Both GDI and CPC significantly decrease IOP in eyes with glaucoma after DSAEK. GDI is preferable to CPC in refractory glaucoma cases after DSAEK, as it manifests a significantly higher success rate for IOP control, similar endothelial graft failure rate, and relatively preserves BCVA than CPC.

[Mandibular condyle localization in orthognathic surgery based on mandibular movement trajectory and its preliminary accuracy verification].

OBJECTIVE: To establish and assess the precision of pre-surgical condyle position planning using mandibular movement trajectory data for orthognathic surgery. METHODS: Skull data from large-field cone beam computed tomography (CBCT) and dental oral scan data were imported into IVSPlan 1.0.25 software for 3D reconstruction and fusion, creating 3D models of the maxilla and mandible. Trajectory data of mandibular movement were collected using a mandibular motion recorder, and the data were integrated with the jaw models within the software. Subsequently, three-dimensional trajectories of the condyle were obtained through matrix transformations, rendering them visually accessible. A senior oral and maxillofacial surgeon with experience in both diagnosis and treatment of temporomandibular joint disease and orthognathic surgery selected the appropriate condyle position using the condyle movement trajectory interface. During surgical design, the mobile mandibular proximal segment was positioned accordingly. Routine orthognathic surgical planning was completed by determining the location of the mandibular distal segment, which was based on occlusal relationships with maxilla and facial aesthetics. A virtual mandible model was created by integrating data from the proximal and distal segment bone. Subsequently, a solid model was generated through rapid prototyping. The titanium plate was pre-shaped on the mandibular model, and the screw hole positions were determined to design a condylar positioning guide device. In accordance with the surgical plan, orthognathic surgery was performed, involving mandibular bilateral sagittal split ramus osteotomy (SSRO). The distal segment of the mandible was correctly aligned intermaxillary, while the proximal bone segment was positioned using the condylar positioning guide device and the pre-shaped titanium plate. The accuracy of this procedure was assessed in a study involving 10 patients with skeletal class Ⅱ malocclusion. Preoperative condyle location planning and intraoperative positioning were executed using the aforementioned techniques. CBCT data were collected both before the surgery and 2 weeks after the procedure, and the root mean square (RMS) distance between the preope-rative design position and the actual postoperative condyle position was analyzed. RESULTS: The RMS of the condyle surface distance measured was (1.59±0.36) mm (95%CI: 1.35-1.70 mm). This value was found to be significantly less than 2 mm threshold recommended by the expert consensus (P < 0.05). CONCLUSION: The mandibular trajectory may play a guiding role in determining the position of the mandibular proximal segment including the condyle in the orthognathic surgery. Through the use of a condylar positioning guide device and pre-shaped titanium plates, the condyle positioning can be personalized and customized with clinically acceptable accuracy.

The role of probiotics in women's health: An update narrative review.

Probiotics, live microorganisms that confer health benefits to the host when administered in adequate amounts, have gained considerable attention for their potential role in maintaining women's health. This overview summarizes key clinical findings on the beneficial effects of probiotics in various aspects of women's health. Probiotics, particularly Lactobacillus species, contribute to vaginal health by promoting a balanced vaginal microbiome to prevent infections and maintain an acidic environment. In gynecologic conditions, probiotics show potential in preventing and managing bacterial vaginosis, vulvovaginal candidiasis, and sexually transmitted infections. Probiotic supplementation has also been associated with improvements in metabolic parameters and menstrual irregularities in polycystic ovary syndrome patients. During pregnancy, probiotics may be helpful in reducing the risk of gestational diabetes, maternal group B streptococcal colonization, obstetric anemia, and postpartum mastitis. In recent years, the potential role of probiotics in the prevention and management of gynecologic cancer has gained attention. Further research is needed to better understand the specific mechanisms and determine the optimal Lactobacillus strains and dosages regimens for gynecologic cancer prevention and therapy. In conclusion, probiotics offer a non-invasive and cost-effective approach to support women's health and prevent obstetric and gynecologic complications.

Targeting tumor-associated macrophages: Novel insights into immunotherapy of skin cancer.

BACKGROUND: The incidence of skin cancer is currently increasing, and conventional treatment options inadequately address the demands of disease management. Fortunately, the recent rapid advancement of immunotherapy, particularly immune checkpoint inhibitors (ICIs), has ushered in a new era for numerous cancer patients. However, the efficacy of immunotherapy remains suboptimal due to the impact of the tumor microenvironment (TME). Tumor-associated macrophages (TAMs), a major component of the TME, play crucial roles in tumor invasion, metastasis, angiogenesis, and immune evasion, significantly impacting tumor development. Consequently, TAMs have gained considerable attention in recent years, and their roles have been extensively studied in various tumors. However, the specific roles of TAMs and their regulatory mechanisms in skin cancer remain unclear. AIM OF REVIEW: This paper aims to elucidate the origin and classification of TAMs, investigate the interactions between TAMs and various immune cells, comprehensively understand the precise mechanisms by which TAMs contribute to the pathogenesis of different types of skin cancer, and finally discuss current strategies for targeting TAMs in the treatment of skin cancer. KEY SCIENTIFIC CONCEPTS OF OVERVIEW: With a specific emphasis on the interrelationship between TAMs and skin cancer, this paper posits that therapeutic modalities centered on TAMs hold promise in augmenting and harmonizing with prevailing clinical interventions for skin cancer, thereby charting a novel trajectory for advancing the landscape of immunotherapeutic approaches for skin cancer.