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Tumor-associated inflammation drives cancer progression and therapy resistance, often linked to the infiltration of monocyte-derived tumor-associated macrophages (TAMs), which are associated with poor prognosis in various cancers. To advance immunotherapies, testing on immunocompetent pre-clinical models of human tissue is crucial. We have developed an in vitro model of microvascular networks with tumor spheroids or patient tissues to assess monocyte trafficking into tumors and evaluate immunotherapies targeting the human tumor microenvironment. Our findings demonstrate that macrophages in vascularized breast and lung tumor models can enhance monocyte recruitment via CCL7 and CCL2, mediated by CSF-1R. Additionally, a multispecific antibody targeting CSF-1R, CCR2, and neutralizing TGF-ß (CSF1R/CCR2/TGF-ß Ab) repolarizes TAMs towards an anti-tumoral M1-like phenotype, reduces monocyte chemoattractant protein secretion, and blocks monocyte migration. This antibody also inhibits monocyte recruitment in patient-specific vascularized tumor models. In summary, this vascularized tumor model recapitulates the monocyte recruitment cascade, enabling functional testing of innovative therapeutic antibodies targeting TAMs in the tumor microenvironment.
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BACKGROUND: Implantable cardioverter-defibrillators (ICDs) and cardiac resynchronization therapy defibrillators (CRT-D) are lifesaving treatments for patients at risk for sudden cardiac death. Effective physician-patient communication during the shared decision-making process is essential. Electrophysiologist-patient conversations were targeted to obtain objective data on the interaction, understand the conversation framework, and uncover opportunities for improved communication. METHODS: Individuals previously identified as requiring an ICD/CRT-D but declined implantation were recruited for this four-stage interview and survey-based study. Quantitative analysis of surveys and AI analysis of conversation videos was conducted to evaluate patient participant expectations, analyze feedback about the conversations with study physicians, and gauge willingness for device implantation. RESULTS: The study included 27 patients (mean age 51 years, 51.9% female) and 9 study physicians. Patients were significantly more willing to undergo ICD/CRT-D implantation after conversing with study physicians compared to their own physicians and pre-conversation surveys (mean scores: 5.0, 3.1, and 4.4 out of 7, respectively; p < 0.001). Patient participants had higher satisfaction with the study conversation, rating study physicians higher in effectiveness of explanations, responsiveness to questions, and overall quality of the conversation compared to their own physicians (all p < 0.001). CONCLUSIONS: In a cohort of patients who previously declined ICD/CRT-D implantation, patient satisfaction and willingness to undergo implantation of a guideline-directed device therapy increased significantly following a structured conversation with study physicians. Identified key elements could be integrated into user-friendly tools and educational materials to facilitate these conversations, improving patient engagement with the decision-making process and enhancing informed acceptance of indicated device therapies.
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BACKGROUND: PINNACLE FLX (Protection Against Embolism for Nonvalvular AF Patients: Investigational Device Evaluation of the WATCHMAN FLX LAA Closure Technology) demonstrated improved outcomes and low incidence of adverse events with the WATCHMAN FLX device in a controlled setting. The National Cardiovascular Disease Registry's Left Atrial Appendage Occlusion Registry was utilized to assess the safety and effectiveness of WATCHMAN FLX in contemporary clinical practice in the United States. METHODS: The WATCHMAN FLX Device Surveillance Post Approval Analysis Plan used data from the Left Atrial Appendage Occlusion registry to identify patients undergoing WATCHMAN FLX implantation between August 2020 and September 2022. The key safety end point was defined as all-cause death, ischemic stroke, systemic embolism, or device or procedure-related events requiring open cardiac surgery or major endovascular intervention between device implantation and hospital discharge. Major adverse events were reported at hospital discharge, 45 days, and 1 year. RESULTS: Among 97 185 patients in the Left Atrial Appendage Occlusion registry undergoing WATCHMAN FLX, successful implantation occurred in 97.5% (n=94 784) of patients. The key safety end point occurred in 0.45% of patients. At 45 days post-procedure, all-cause death occurred in 0.81% patients, ischemic stroke in 0.23%, major bleeding in 3.1%, pericardial effusion requiring intervention in 0.50%, device-related thrombus in 0.44%, and device embolism in 0.04% patients. No peri-device leak was observed in 83.1% of patients at 45 days. At 1 year, the rate of all-cause death was 8.2%, the rate of any stroke was 1.5% (ischemic stroke, 1.2%), and major bleeding occurred in 6.4% of patients. CONCLUSIONS: In a large contemporary cohort of patients with the WATCHMAN FLX device, the rates of implant success and clinical outcomes through 1 year were comparable with the PINNACLE FLX study, demonstrating that favorable outcomes achieved in the pivotal approval study can be replicated in routine clinical practice.
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Fibrilação Atrial , Flutter Atrial , Ablação por Cateter , Veias Pulmonares , Humanos , Flutter Atrial/cirurgia , Flutter Atrial/fisiopatologia , Flutter Atrial/etiologia , Fibrilação Atrial/cirurgia , Fibrilação Atrial/fisiopatologia , Veias Pulmonares/cirurgia , Ablação por Cateter/efeitos adversos , Masculino , Pessoa de Meia-Idade , Eletrocardiografia , Idoso , FemininoRESUMO
CRISPR prime editing offers unprecedented versatility and precision for the installation of genetic edits in situ . Here we describe the development and characterization of the Multiplexing Of Site-specific Alterations for In situ Characterization ( MOSAIC ) method, which leverages a non-viral PCR-based prime editing method to enable rapid installation of thousands of defined edits in pooled fashion. We show that MOSAIC can be applied to perform in situ saturation mutagenesis screens of: (1) the BCR-ABL1 fusion gene, successfully identifying known and potentially new imatinib drug-resistance variants; and (2) the IRF1 untranslated region (UTR), re-confirming non-coding regulatory elements involved in transcriptional initiation. Furthermore, we deployed MOSAIC to enable high-throughput, pooled screening of hundreds of systematically designed prime editing guide RNA ( pegRNA ) constructs for a large series of different genomic loci. This rapid screening of >18,000 pegRNA designs identified optimized pegRNAs for 89 different genomic target modifications and revealed the lack of simple predictive rules for pegRNA design, reinforcing the need for experimental optimization now greatly simplified and enabled by MOSAIC. We envision that MOSAIC will accelerate and facilitate the application of CRISPR prime editing for a wide range of high-throughput screens in human and other cell systems.
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Current technologies for upregulation of endogenous genes use targeted artificial transcriptional activators but stable gene activation requires persistent expression of these synthetic factors. Although general "hit-and-run" strategies exist for inducing long-term silencing of endogenous genes using targeted artificial transcriptional repressors, to our knowledge no equivalent approach for gene activation has been described to date. Here we show stable gene activation can be achieved by harnessing endogenous transcription factors ( EndoTF s) that are normally expressed in human cells. Specifically, EndoTFs can be recruited to activate endogenous human genes of interest by using CRISPR-based gene editing to introduce EndoTF DNA binding motifs into a target gene promoter. This Precision Editing of Regulatory Sequences to Induce Stable Transcription-On ( PERSIST-On ) approach results in stable long-term gene activation, which we show is durable for at least five months. Using a high-throughput CRISPR prime editing pooled screening method, we also show that the magnitude of gene activation can be finely tuned either by using binding sites for different EndoTF or by introducing specific mutations within such sites. Our results delineate a generalizable framework for using PERSIST-On to induce heritable and fine-tunable gene activation in a hit-and-run fashion, thereby enabling a wide range of research and therapeutic applications that require long-term upregulation of a target gene.
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We present an unusual case of alternating left anterior and left posterior fascicular block. Given the known risk for progression to complete atrioventricular block with alternating right bundle and left bundle branch block, we performed an electrophysiological study. Findings were consistent with infra-Hisian disease, and the patient underwent pacemaker implantation.
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Background: Respiratory motion management strategies are used to minimize the effects of breathing on the precision of stereotactic ablative radiotherapy for ventricular tachycardia, but the extent of cardiac contractile motion of the human heart has not been systematically explored. Objective: We aim to assess the magnitude of cardiac contractile motion between different directions and locations in the heart. Methods: Patients with intracardiac leads or valves who underwent 4-dimensional cardiac computed tomography (CT) prior to a catheter ablation procedure for atrial or ventricular arrhythmias at 2 medical centers were studied retrospectively. The displacement of transvenous right atrial appendage, right ventricular (RV) implantable cardioverter-defibrillator, coronary sinus lead tips, and prosthetic cardiac devices across the cardiac cycle were measured in orthogonal 3-dimensional views on a maximal-intensity projection CT reconstruction. Results: A total of 31 preablation cardiac 4-dimensional cardiac CT scans were analyzed. The LV lead tip had significantly greater motion compared with the RV lead in the anterior-posterior direction (6.0 ± 2.2 mm vs 3.8 ± 1.7 mm; P = .01) and superior-inferior direction (4.4 ± 2.9 mm vs 3.5 ± 2.0 mm; P = .049). The prosthetic aortic valves had the least movement of all fiducials, specifically compared with the RV lead tip in the left-right direction (3.2 ± 1.2 mm vs 6.1 ± 3.8 mm, P = .04) and the LV lead tip in the anterior-posterior direction (3.8 ± 1.7 mm vs 6.0 ± 2.2 mm, P = .03). Conclusion: The degree of cardiac contractile motion varies significantly (1 mm to 15.2 mm) across different locations in the heart. The effect of contractile motion on the precision of radiotherapy should be assessed on a patient-specific basis.
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INTRODUCTION: Artificial intelligence (AI) ECG arrhythmia mapping provides arrhythmia source localization using 12-lead ECG data; whether this information impacts procedural efficiency is unknown. We performed a retrospective, case-control study to evaluate the hypothesis that AI ECG mapping may reduce time to ablation, procedural duration, and fluoroscopy. MATERIALS AND METHODS: Cases in which system output was used were retrospectively enrolled according to IRB-approved protocols at each site. Matched control cases were enrolled in reverse chronological order beginning on the last day for which the technology was unavailable. Controls were matched based upon physician, institution, arrhythmia, and a predetermined complexity rating. Procedural metrics, fluoroscopy data, and clinical outcomes were assessed from time-stamped medical records. RESULTS: The study group consisted of 28 patients (age 65 ± 11 years, 46% female, left atrial dimension 4.1 ± 0.9 cm, LVEF 50 ± 18%) and was similar to 28 controls. The most common arrhythmia types were atrial fibrillation (n = 10), premature ventricular complexes (n = 8), and ventricular tachycardia (n = 6). Use of the system was associated with a 19.0% reduction in time to ablation (133 ± 48 vs. 165 ± 49 min, p = 0.02), a 22.6% reduction in procedure duration (233 ± 51 vs. 301 ± 83 min, p < 0.001), and a 43.7% reduction in fluoroscopy (18.7 ± 13.3 vs. 33.2 ± 18.0 min, p < 0.001) versus controls. At 6 months follow-up, arrhythmia-free survival was 73.5% in the study group and 63.3% in the control group (p = 0.56). CONCLUSION: Use of forward-solution AI ECG mapping is associated with reductions in time to first ablation, procedure duration, and fluoroscopy without an adverse impact on procedure outcomes or complications.
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Potenciais de Ação , Arritmias Cardíacas , Inteligência Artificial , Ablação por Cateter , Valor Preditivo dos Testes , Tempo para o Tratamento , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Arritmias Cardíacas/fisiopatologia , Arritmias Cardíacas/diagnóstico , Arritmias Cardíacas/cirurgia , Ablação por Cateter/efeitos adversos , Eletrocardiografia , Técnicas Eletrofisiológicas Cardíacas , Fluoroscopia , Frequência Cardíaca , Duração da Cirurgia , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento , Estudos de Casos e ControlesRESUMO
BACKGROUND: The effect of contact force (CF) on lesion formation is not clear during pulsed field ablation (PFA). The aim of this study was to evaluate the impact of CF, PFA, and their interplay through the PFA index (PF index) formula on the ventricular lesion size in swine. METHODS: PFA was delivered through the CF-sensing OMNYPULSE catheter. Predefined PFA applications (×3, ×6, ×9, and ×12) were delivered maintaining low (5-25 g), high (26-50 g), and very high (51-80 g) CFs. First, PFA lesions were evaluated on necropsy in 11 swine to investigate the impact of CF/PFA-and their integration in the PF index equation-on lesion size (study characterization). Then, 3 different PF index thresholds-300, 450, and 600-were tested in 6 swine to appraise the PF index accuracy to predict the ventricular lesion depth (study validation). RESULTS: In the study characterization data set, 111 PFA lesions were analyzed. CF was 32±17 g. The average lesion depth and width were 3.5±1.2 and 12.0±3.5 mm, respectively. More than CF and PFA dose alone, it was their combined effect to impact lesion depth through an asymptotically increasing relationship. Likewise, not only was the PF index related to lesion depth in the study validation data set (r2=0.66; P<0.001) but it also provided a prediction accuracy of the observed depth of ±2 mm in 69/73 lesions (95%). CONCLUSIONS: CF and PFA applications play a key role in lesion formation during PFA. Further studies are required to evaluate the best PFA ablation settings to achieve transmural lesions.
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Ablação por Cateter , Suínos , Animais , Ablação por Cateter/efeitos adversos , Ventrículos do Coração/cirurgia , Catéteres , Desenho de EquipamentoRESUMO
BACKGROUND: The National Cardiovascular Data Registry Left Atrial Appendage Occlusion Registry (LAAO) includes the vast majority of transcatheter LAAO procedures performed in the United States. The objective of this study was to develop a model predicting adverse events among patients undergoing LAAO with Watchman FLX. METHODS: Data from 41â 001 LAAO procedures with Watchman FLX from July 2020 to September 2021 were used to develop and validate a model predicting in-hospital major adverse events. Randomly selected development (70%, n=28â 530) and validation (30%, n=12â 471) cohorts were analyzed with 1000 bootstrapped samples, using forward stepwise logistic regression to create the final model. A simplified bedside risk score was also developed using this model. RESULTS: Increased age, female sex, low preprocedure hemoglobin, no prior attempt at atrial fibrillation termination, and increased fall risk most strongly predicted in-hospital major adverse events and were included in the final model along with other clinically relevant variables. The median in-hospital risk-standardized adverse event rate was 1.50% (range, 1.03%-2.84%; interquartile range, 1.42%-1.64%). The model demonstrated moderate discrimination (development C-index, 0.67 [95% CI, 0.65-0.70] and validation C-index, 0.66 [95% CI, 0.62-0.70]) with good calibration. The simplified risk score was well calibrated with risk of in-hospital major adverse events ranging from 0.26% to 3.90% for a score of 0 to 8, respectively. CONCLUSIONS: A transcatheter LAAO risk model using National Cardiovascular Data Registry and LAAO Registry data can predict in-hospital major adverse events, demonstrated consistency across hospitals and can be used for quality improvement efforts. A simple bedside risk score was similarly predictive and may inform shared decision-making.
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Apêndice Atrial , Fibrilação Atrial , Acidente Vascular Cerebral , Humanos , Feminino , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/prevenção & controle , Apêndice Atrial/cirurgia , Estudos Retrospectivos , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/cirurgia , Fatores de Risco , Resultado do TratamentoRESUMO
BACKGROUND: Metastasis to the hyoid bone is an exceptionally rare occurrence, with documented cases limited to breast, liver, colon, skin, lung, and prostate cancers. This report highlights an unusual case involving the metastasis of lung adenocarcinoma to the hyoid bone, accompanied by a distinctive headache. Previous documentation involved surgical resection of the hyoid mass. We present a case displaying the benefits of palliative radiotherapy. CASE SUMMARY: A 72-year-old non-smoking, non-alcoholic woman, initially under investigation for a year-long elevation in absolute lymphocyte count, presented with a month-long history of intermittent throat pain. Despite negative findings in gastroenterological and otolaryngologic examinations, a contrast-enhanced chest computed tomography scan revealed a mediastinal mass and questionable soft tissue thickening in her left anterolateral neck. Subsequent imaging and biopsies confirmed the presence of lung adenocarcinoma metastasis to the hyoid bone. The patient was treated with platinum-based chemo-immunotherapy along with pembrolizumab. Ultimately, the lung cancer was unresponsive. Our patient opted for palliative radiation therapy instead of surgical resection to address her throat pain. As a result, her throat pain was alleviated, and it also incidentally resolved her chronic headaches. This is the second documented case of lung adenocarcinoma metastasizing to the hyoid bone. CONCLUSION: Palliative radiotherapy may add to the quality of life in symptomatic patients with cancer metastatic to the hyoid bone.
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BACKGROUND: Frailty is associated with significant morbidity and mortality and may have clinical implications in an advanced age population with atrial fibrillation undergoing left atrial appendage occlusion (LAAO). We sought to develop a novel frailty scale to predict worse outcomes in patients undergoing LAAO. METHODS: Patients in the NCDR LAAO Registry between 2016 and 2021 receiving percutaneous LAAO devices were categorized as non-frail (0 points), pre-frail (1-3 points), or frail (4-5 points) based on a 5-point scale representing multiple domains of frailty: hemoglobin <13.0 g/dL in male, <12.0 g/dL in female; creatinine ≥1.2 mg/dL; albumin <3.5 g/dL; body mass index <20 kg/m2; and increased risk of falls. RESULTS: Of 57,728 patients, 44,360 (76.8%) were pre-frail and 7693 (13.3%) were frail. Compared to non-frail, pre-frail and frail patients were older, had a higher burden of co-morbidities, and more disability based on the Modified Rankin Scale. Compared to non-frail patients after adjustment, frail patients were at higher risk of in-hospital major complication (OR 1.29, 95% 1.02-1.62, p = 0.01), any complication (OR 1.29, 95% CI 1.09-1.52, p = 0.0005), and death (OR 5.79, 95% CI 1.75-19.17, p = 0.001), while no difference was observed in pre-frail patients. At 45-day follow-up, there was no difference in the risk of complications in frail patients as compared to non-frail, although mortality was significantly higher (OR 3.01, 95% CI 1.97-4.85, p < 0.0001). CONCLUSION: A simple and practical frailty scale accurately predicts adverse events in patients undergoing LAAO. The 13% of patients considered frail were at significantly higher risk of in-hospital adverse events and 45-day mortality.
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Apêndice Atrial , Fibrilação Atrial , Fragilidade , Acidente Vascular Cerebral , Humanos , Masculino , Feminino , Apêndice Atrial/diagnóstico por imagem , Apêndice Atrial/cirurgia , Fragilidade/epidemiologia , Fragilidade/complicações , Estudos Retrospectivos , Sistema de Registros , Acidente Vascular Cerebral/etiologia , Resultado do TratamentoRESUMO
BACKGROUND: Pulsed field ablation (PFA) induces cell death through electroporation using ultrarapid electrical pulses. We sought to compare the procedural efficiency characteristics, safety, and efficacy of ablation of atrial fibrillation (AF) using PFA compared with thermal energy ablation. METHODS: We performed an extensive literature search and systematic review of studies that compared ablation of AF with PFA versus thermal energy sources. Risk ratio (RR) 95% confidence intervals (CI) were measured for dichotomous variables and mean difference (MD) 95% CI were measured for continuous variables, where RR < 1 and MD < 0 favor the PFA group. RESULTS: We included 6 comparative studies for a total of 1012 patients who underwent ablation of AF: 43.6% with PFA (n = 441) and 56.4% (n = 571) with thermal energy sources. There were significantly shorter procedures times with PFA despite a protocolized 20-min dwell time (MD - 21.95, 95% CI - 33.77, - 10.14, p = 0.0003), but with significantly longer fluroscopy time (MD 5.71, 95% CI 1.13, 10.30, p = 0.01). There were no statistically significant differences in periprocedural complications (RR 1.20, 95% CI 0.59-2.44) or recurrence of atrial tachyarrhythmias (RR 0.64, 95% CI 0.31, 1.34) between the PFA and thermal ablation cohorts. CONCLUSIONS: Based on the results of this meta-analysis, PFA was associated with shorter procedural times and longer fluoroscopy times, but no difference in periprocedural complications or rates of recurrent AF when compared to ablation with thermal energy sources. However, larger randomized control trials are needed.
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Fibrilação Atrial , Ablação por Cateter , Veias Pulmonares , Humanos , Fibrilação Atrial/cirurgia , Ablação por Cateter/métodos , Átrios do Coração/cirurgia , Resultado do Tratamento , Veias Pulmonares/cirurgiaRESUMO
Nonvalvular atrial fibrillation is a common rhythm disorder of middle-aged to older adults that can cause ischemic strokes and systemic embolism. Lifelong use of oral anticoagulants reduces the risk of these ischemic events but increases the risk of major and clinically relevant hemorrhages. These medications also require strict compliance for efficacy, and they have nontrivial failure rates in higher-risk patients. Left atrial appendage closure is a nonpharmacological method to prevent ischemic strokes in atrial fibrillation without the need for lifelong anticoagulant use, but this procedure has the potential for complications and residual embolic events. This workshop of the Roundtable of Academia and Industry for Stroke Prevention discussed future research needed to further decrease the ischemic and hemorrhagic risks among patients with atrial fibrillation. A direct thrombin inhibitor, factor Xa inhibitors, and left atrial appendage closure are FDA-approved approaches whereas factor XIa inhibitors are currently being studied in phase 3 randomized controlled trials for stroke prevention. The benefits, risks, and shortcomings of these treatments and future research required in different high-risk patient populations are reviewed in this consensus statement.
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Apêndice Atrial , Fibrilação Atrial , Embolia , AVC Isquêmico , Acidente Vascular Cerebral , Pessoa de Meia-Idade , Humanos , Idoso , Fibrilação Atrial/complicações , Fibrilação Atrial/tratamento farmacológico , Acidente Vascular Cerebral/prevenção & controle , Acidente Vascular Cerebral/complicações , Anticoagulantes/uso terapêutico , Embolia/complicações , AVC Isquêmico/tratamento farmacológico , Resultado do TratamentoRESUMO
Clonotypic αß T cell responses to cargoes presented by major histocompatibility complex (MHC), MR1, or CD1 proteins underpin adaptive immunity. Those responses are mostly mediated by complementarity-determining region 3 motifs created by quasi-random T cell receptor (TCR) gene rearrangements, with diversity being highest for TCRγδ. Nonetheless, TCRγδ also displays nonclonotypic innate responsiveness following engagement of germline-encoded Vγ-specific residues by butyrophilin (BTN) or BTN-like (BTNL) proteins that uniquely mediate γδ T cell subset selection. We now report that nonclonotypic TCR engagement likewise induces distinct phenotypes in TCRαß+ cells. Specifically, antibodies to germline-encoded human TCRVß motifs consistently activated naïve or memory T cells toward core states distinct from those induced by anti-CD3 or superantigens and from others commonly reported. Those states combined selective proliferation and effector function with activation-induced inhibitory receptors and memory differentiation. Thus, nonclonotypic TCRVß targeting broadens our perspectives on human T cell response modes and might offer ways to induce clinically beneficial phenotypes in defined T cell subsets.
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Receptores de Antígenos de Linfócitos T alfa-beta , Receptores de Antígenos de Linfócitos T gama-delta , Humanos , Receptores de Antígenos de Linfócitos T alfa-beta/genética , Subpopulações de Linfócitos T , Butirofilinas/genética , Butirofilinas/metabolismo , Fenótipo , ImunoterapiaRESUMO
Tumor-associated inflammation drives cancer progression and therapy resistance, with the infiltration of monocyte-derived tumor-associated macrophages (TAMs) associated with poor prognosis in diverse cancers. Targeting TAMs holds potential against solid tumors, but effective immunotherapies require testing on immunocompetent human models prior to clinical trials. Here, we develop an in vitro model of microvascular networks that incorporates tumor spheroids or patient tissues. By perfusing the vasculature with human monocytes, we investigate monocyte trafficking into the tumor and evaluate immunotherapies targeting the human tumor microenvironment. Our findings demonstrate that macrophages in vascularized breast and lung tumor models can enhance monocyte recruitment via TAM-produced CCL7 and CCL2, mediated by CSF-1R. Additionally, we assess a novel multispecific antibody targeting CCR2, CSF-1R, and neutralizing TGF-ß, referred to as CSF1R/CCR2/TGF-ß Ab, on monocytes and macrophages using our 3D models. This antibody repolarizes TAMs towards an anti-tumoral M1-like phenotype, reduces monocyte chemoattractant protein secretion, and effectively blocks monocyte migration. Finally, we show that the CSF1R/CCR2/TGF-ß Ab inhibits monocyte recruitment in patient-specific vascularized tumor models. Overall, this vascularized tumor model offers valuable insights into monocyte recruitment and enables functional testing of innovative therapeutic antibodies targeting TAMs in the tumor microenvironment (TME).