Search Results (543)

Preeclampsia (PE) is a severe pregnancy-specific hypertensive disorder characterized by immune microenvironment dysregulation at the maternal–fetal interface, with decidual macrophage phenotypic imbalance being a key pathological feature. The Ghrelin/growth hormone secretagogue receptor-1a (GHSR-1a) axis exerts immunomodulatory and anti-inflammatory effects, but its role in regulating decidual macrophage infiltration and phenotypic marker expression in PE remains unclear. In this study, we first detected the expression of the Ghrelin/GHSR-1a axis in decidual tissues from 10 healthy pregnant women and 12 PE patients via immunohistochemistry (IHC). We then established a lipopolysaccharide (LPS)-induced PE-like rat model to investigate the axis’s functional role and underlying mechanisms. Intriguingly, clinical analysis revealed a severity-dependent compensatory escalation of the Ghrelin/GHSR-1a axis in PE decidual tissues, potentially representing an endogenous antagonistic response to pregnancy-associated pathological stress. In the animal model, exogenous Ghrelin supplementation reversed LPS-induced PE-like phenotypes, including hypertension, proteinuria, fetal growth restriction (FGR), and placental dysfunction, and alleviated pathological damage to the maternal liver, kidney, and placenta. Mechanistically, Ghrelin modulated decidual macrophage phenotypic marker expression by downregulating the M1 marker CD86 and upregulating the M2 marker CD163 and promoted trophoblast invasion and spiral artery remodeling by restoring laminin, α-cytokeratin 7 (α-CK7), and α-smooth muscle actin (α-SMA) expression in placental tissue. All protective effects of Ghrelin were abrogated by co-administration of D-lys-3-GHRP-6, a specific GHSR-1a antagonist, confirming the dependence on the Ghrelin/GHSR-1a axis. Collectively, our findings suggest that the Ghrelin/GHSR-1a axis is compensatorily upregulated in PE and may exert a protective role by regulating decidual macrophage phenotypic marker expression and improving placental function, providing preliminary evidence that this axis merits further investigation as a potential research target for PE. Full article

Kidney transplantation remains the optimal treatment for end-stage renal disease, yet long-term allograft survival has plateaued due to persistent rejection. This review provides a comprehensive overview of the inflammatory and immune pathways implicated in kidney allograft rejection, integrating current evidence from basic and translational research. Ischemia–reperfusion injury initiates an inflammatory cascade through the release of damage-associated molecular patterns, activating Toll-like receptors and the complement system, thereby priming the alloimmune response. Innate immune cells, including macrophages, dendritic cells, and natural killer cells, bridge sterile tissue injury to adaptive alloimmunity, while the emerging concept of trained immunity reveals long-lasting epigenetic reprogramming of monocytes with direct implications for graft longevity. The adaptive response encompasses T cell-mediated rejection, driven by Th1, Th17, and CD8⁺ cytotoxic lymphocytes, and antibody-mediated rejection, mediated by donor-specific antibodies through complement activation and antibody-dependent cellular cytotoxicity. Key signalling pathways, including JAK-STAT, NF-κB, NLRP3 inflammasome, and mTOR, amplify allograft inflammation and promote progression toward chronic injury. Macrophage polarisation and macrophage-to-myofibroblast transition have been identified as major drivers of interstitial fibrosis and late graft failure. Recent advances in non-invasive biomarkers, such as donor-derived cell-free DNA and molecular phenotyping, are transforming rejection diagnostics. Emerging therapies, including costimulation blockade, anti-CD38 antibodies, complement inhibitors, and regulatory T cell-based approaches, offer the potential to shift transplant medicine toward precision-guided, tolerance-inducing strategies. This review synthesises these developments and discusses future perspectives for improving long-term allograft outcomes. Full article

Background/Objectives: This study aimed to develop a novel tumor-associated macrophage (TAM)-targeting nanoplatform to improve the solubility and bioavailability of camptothecin (CPT) and achieve active targeted drug delivery for enhanced anti-tumor immunotherapy. Methods: We constructed a sialic acid-disulfide bond-camptothecin (SA-SS-CPT) nanowire system. Sialic acid was used as a targeting ligand to specifically recognize the overexpressed Siglec-E receptor on TAMs. Upon cellular internalization, the disulfide bond was designed to respond to intracellular glutathione (GSH), enabling controlled drug release. Results: The SA-SS-CPT nanowires significantly improved CPT solubility and enabled targeted delivery to TAMs. Following GSH-responsive cleavage and CPT release, the nanowires induced DNA damage in TAMs, activating the cGAS-STING signaling pathway. This promoted TAM polarization toward the M1 phenotype, enhanced pro-inflammatory and anti-tumor immune responses, and inhibited tumor immune escape. Furthermore, SA-SS-CPT synergistically improved the efficacy of PD-L1 blockade immunotherapy, remodeling the tumor immune microenvironment. Conclusions: The SA-SS-CPT nanoplatform effectively targets TAMs, repolarizes them to an anti-tumor M1 phenotype, and activates the cGAS-STING pathway. It shows strong potential for overcoming tumor immune escape and synergizing with PD-L1 checkpoint blockade to achieve significant tumor clearance. Full article

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder, which has recently been found to be closely associated with neuroinflammation. As an anti-inflammatory drug, triptolide (TP), a natural diterpenoid from Tripterygium wilfordii, was selected in the current study for treating PS19 (tau^P301S transgenic) mice, tauopathy AD mice. In addition, we have previously found that TP had the ability to reduce the level of cholesterol. However, the roles and mechanisms of TP in the above processes are not clear. To this end, we found that elevated cholesterol in serum and brain tissues upregulated the expression of apolipoprotein E (APOE) and sialic acid-binding Ig-like lectin 3 (CD33), leading to the activation of SH2-containing protein tyrosine phosphatase 1 (SHP-1). The activation of SHP-1 inhibits the signaling pathways of Janus kinase 1 (JAK1) and signal transducer and activator of transcription 6 (STAT6), which results in inhibition of the M2 polarization of microglia, which exacerbates neuroinflammation and cognitive decline in high-cholesterol diet (HCD)-fed mice. Conversely, TP treatment significantly inhibited the hepatic sterol regulatory element-binding protein 2 (SREBP2)/3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) pathway, which reduced the cholesterol levels in the serum and brain. By depressing the levels of cholesterol, the axis of CD33 and SHP-1 was suppressed, which resulted in restoration of the activity of JAK1 and STAT6 pathways, leading to the transition of microglia from the M1 to the M2 phenotype. Of note, these observations demonstrate that TP alleviates the cognitive impairment of PS19 mice via depressing neuroinflammation. Altogether, our results revealed the mechanisms of TP in treating AD via CD33/SHP-1/JAK1/STAT6 pathways in a cholesterol-dependent manner. Full article

This translational synthesis highlights the potential role of obesity-induced low-grade chronic inflammation in modulating clinical outcomes among patients with spondyloarthritis (SpA). Obesity transforms adipose tissue into a pro-inflammatory endocrine organ, where hypertrophic adipocytes release adipokines such as leptin alongside cytokines including TNF-α and IL-6, potentially contributing to macrophage polarization toward an M1 phenotype and activating NF-κB signaling pathways. This systemic immunometabolic priming may lower activation thresholds at the enthesis—the primary pathological site in SpA—potentially amplifying IL-23/IL-17 axis activity via Th17 bias, innate-like lymphocyte responses, and stromal–immune crosstalk under mechanical stress. Clinically, patients with SpA and obesity have been reported to demonstrate heightened disease activity (BASDAI, ASDAS), impaired function (BASFI), accelerated radiographic progression (syndesmophytes, enthesophytes), and diminished biologic response rates, potentially attributable to pharmacokinetic alterations (e.g., subtherapeutic TNF inhibitor levels) and pharmacodynamic resistance. Multisystem comorbidities, including non-alcoholic fatty liver disease, cardiovascular events, metabolic syndrome, sleep disturbances, and depression, further exacerbate morbidity and diminish quality of life. Therapeutic implications emphasize obesity as a modifiable disease modifier. Weight loss interventions, including hypocaloric diets, anti-inflammatory regimens (e.g., Mediterranean diet), multicomponent exercise, GLP-1 receptor agonists, and bariatric surgery, have been associated with reductions in inflammatory biomarkers, improved remission rates (MDA, DAPSA), and prolonged drug survival by restoring adipokine balance and disrupting mechano-inflammatory loops. Future randomized controlled trials should prioritize long-term evaluations of integrated multidisciplinary strategies that combine metabolic optimization with immunomodulatory therapies, addressing adherence challenges through psychological support and patient-tailored protocols, while elucidating dose–response relationships for GLP-1RAs and exercise in diverse SpA subtypes to establish precision management paradigms that mitigate cardiometabolic burden and improve holistic outcomes. Full article

Influenza A virus (IAV) remains a major global health threat despite available vaccines and antiviral agents, while current therapies are limited by drug resistance and safety concerns. Curcuminoids exhibit antiviral and anti-inflammatory activities but are constrained by poor water solubility and low bioavailability. To address these limitations, we investigated the antiviral and immunomodulatory properties of a water-solubilized curcuminoid nanoparticle formulation (C–S/M) in both in vitro and in vivo models of IAV infection. To evaluate the potential antiviral and anti-inflammatory effects of C–S/M, we performed a cytopathic effect (CPE) reduction assay in triplicate at 0.001 MOI and quantitative real-time PCR (qRT-PCR) targeting viral NS1 transcripts in MDCK cells. C–S/M suppressed viral NS1 vRNA levels in MDCK cells at lower curcuminoid-equivalent concentrations than native curcuminoids and attenuated IAV-induced TNF-α, IL-6, and IL-8 production. Furthermore, in vivo antiviral efficacy was evaluated in female C57BL/6 mice intranasally infected with IAV and treated orally with C–S/M. Survival, lung viral loads, pulmonary cytokine levels, and splenic immune cell phenotypes were analyzed. In IAV-infected mice, oral administration of C–S/M modestly improved survival and significantly reduced lung viral burden and pulmonary proinflammatory cytokine levels. In addition, in vivo C–S/M treatment was associated with recovery of virus-suppressed T-cell immune responses, including increased Th1 and activated CD8⁺ T cells, reduced regulatory T-cell expansion, and restoration of multifunctional CD4⁺ and CD8⁺ T cells. These findings suggest that C–S/M exerts antiviral and immunomodulatory effects in experimental IAV infection and may serve as a potential adjunctive candidate for further investigation against influenza-associated inflammation. Full article

Acute non-typhoidal salmonellosis (NTS) from non-typhoidal Salmonella remains a major cause of foodborne bacterial gastroenteritis, and non-antibiotic interventions are needed to combat multidrug-resistant NTS. Bioactive compounds from edible mushroom extracts have shown both direct and indirect antimicrobial activities on Salmonella. However, the variation in their antimicrobial activity could be due to several factors, including the extract’s form and strain. This study investigated the ability of crude exopolysaccharides (EPs) produced by Schizophyllum commune CMU-01 to limit Salmonella infection in vitro. Agar well diffusion and liquid culture were used to determine the direct anti-Salmonella activity of S. commune EPs, while the gentamicin protection assay and qPCR in human gut epithelium (T84 cells) and murine macrophages (RAW264.7 cells) were used to investigate its indirect (immunomodulatory) activity. Our data reveal that S. commune EPs do not confer the direct antimicrobial property against Salmonella. However, its immunomodulatory activity in two important components of the gut innate defense (the gut epithelium and macrophages) against Salmonella infection has been demonstrated. S. commune EPs reduce Salmonella gut epithelial cell invasion and activate macrophages toward M1 (inflammatory phenotype) polarization, resulting in the reduction in intracellular Salmonella burdens. Alterations in proinflammatory and anti-inflammatory cytokine gene expressions were also detected in S. commune EPs-treated cells. These findings suggest that the host innate immune response to fungal exopolysaccharides derived from S. commune CMU-01 favors reducing Salmonella proliferation within host cells by altering the expression levels of proinflammatory cytokines. Full article

Background/Objectives: Inflammation is a critical contributor to the development of diabetic retinopathy (DR). In the early stages of DR, the compromised permeability of the blood–retina barrier facilitates the infiltration of macrophages and the activation of microglia. These specific retinal immune cells can adopt morphologies M1 or M2, linked to pro- or anti-inflammatory responses, respectively. This dual response represents a new therapeutic target against DR progression. This study aimed to investigate the modulation of the response M1/M2 and the molecular mechanism of two algal diterpenoids, rugukadiol A (RK) and ruguloptone A (RL), in the early inflammatory events associated with DR. Methods: LPS-stimulated microglial (Bv.2) and macrophage (RAW264.7) cells and an ex vivo physiological model of DR were used to analyze the effects of RK and RL on M1 and M2 inflammatory markers. Results: Compounds RK and RL, besides decreasing the expression of the M1 pro-inflammatory factors iNOS, Il6 mRNA, and NLRP3 in LPS-stimulated Bv.2 cells, caused enhancements in Arg-1 mRNA and Il10 mRNA expression consistent with the induction of an M2 anti-inflammatory response. RK promoted p38α-MAPK phosphorylation, suggesting a non-classical activation of p38α related to the induction of anti-inflammatory responses. Consistently, treatment of retinal explants of BB rats in the early stages of DR with RL decreased M1 pro-inflammatory mediators and induced M2 anti-inflammatory markers, with a reduction in gliosis and a phenotype switch from activated to resting microglia. Conclusions: This study provides the first evidence of algal diterpenoids attenuating pro-inflammatory mediators and promoting the resolution of inflammation in a diabetic retinopathy context, thus opening the way to further explore this class of marine natural products and analogs for early DR management. Full article

Once written off as nothing more than a waste product of glycolysis, lactic acid is now seen as a key signaling molecule that operates across a wide range of physiological and pathological processes, from immune regulation and tumor metabolism to neural function. But its role goes beyond energy metabolism and cell signaling. Recent studies have uncovered a new type of post-translational modification called histone lactylation, in which lactate itself provides the lactoyl group attached to lysine residues on histones. This modification directly ties a cell’s metabolic state to the epigenetic control of gene expression. For example, histone lactylation helps shift macrophages from a pro-inflammatory M1 phenotype to an anti-inflammatory M2 phenotype by fine-tuning gene transcription. In this review, we walk through the discovery and biochemical foundation of histone lactylation; discuss the likely writer and eraser enzymes that manage its dynamic changes; and highlight recent advances in understanding the role of this modification in inflammation, tumorigenesis, neurological disorders, and interactions with gut microbes. We also lay out key unanswered questions and consider why targeting protein lactylation might open up new therapeutic possibilities. Full article

Background: Impaired angiogenesis and persistent inflammation are hallmarks of chronic diabetic wounds. Extracellular vesicles derived from dental pulp stem cells (DPSC-EVs) represent a promising cell-free therapy for tissue repair; however, their clinical translation is hindered by suboptimal yields and attenuated bioactivity associated with conventional two-dimensional (2D) culture. This study investigated whether a biomimetic three-dimensional (3D) fibrin/gelatin hydrogel system could optimize the therapeutic potency of DPSC-EVs for diabetic wound healing. Methods: DPSCs were encapsulated within 3D fibrin/gelatin scaffolds, followed by comprehensive characterization of cell viability and morphology. 3D-EVs and 2D-EVs were isolated via ultracentrifugation and validated by transmission electron microscopy and nanoparticle tracking analysis. The pro-angiogenic capacity of 3D-EVs was evaluated using human umbilical vein endothelial cells (HUVECs) under high-glucose (HG) stress. Additionally, the immunomodulatory effects were assessed by monitoring macrophage polarization in lipopolysaccharide-stimulated RAW 264.7 cells. The therapeutic efficacy was further validated in vivo using a streptozotocin (STZ)-induced diabetic mouse model with full-thickness cutaneous wounds. Results: The 3D fibrin/gelatin hydrogel provided a supportive microenvironment that significantly augmented the secretory productivity of DPSCs. Compared to 2D-EVs, 3D-EVs exhibited superior functional resilience in restoring HUVEC migration and tube formation under HG-induced oxidative stress. Furthermore, 3D-EVs effectively orchestrated the macrophage transition from a pro-inflammatory M1 phenotype toward an anti-inflammatory M2 phenotype, thereby modulating the immune microenvironment. In vivo, topical administration of 3D-EVs markedly accelerated wound closure, promoted re-epithelialization, and enhanced microvascular density and collagen maturation in diabetic mice. Conclusions: Our findings demonstrate that the 3D fibrin/gelatin culture system effectively primes the therapeutic profile of DPSC-EVs. These engineered vesicles accelerate diabetic wound healing by synergistically promoting angiogenesis and resolving chronic inflammation, offering a robust and potent cell-free strategy for the management of chronic diabetic ulcers. Full article

Background/Objectives: Idiopathic inflammatory myopathies (IIMs) are chronic immune-mediated disorders, causing striated muscle weakness and extramuscular symptoms. Real-world, single-centre data are needed to interpret phenotype patterns and evolving therapies. Methods: A single-centre, retrospective cohort study was conducted at the Rheumatology Clinic of the National Institute of Geriatrics, Rheumatology and Rehabilitation, Warsaw, Poland from 1 January 2022 to 31 December 2025. Data included demographics, IIM subtypes, extramuscular involvement, co-existing Sjögren disease (SD), biopsy results, autoantibodies, and treatment. Due to sample size, descriptive analysis was used. Results: The study included 35 patients (31.4% men). Mean age was 50.7 years; mean body mass index (BMI) was 26.0 kg/m². The cohort consisted of 10 dermatomyositis (DM), one polymyositis (PM), two immune-mediated necrotising myopathy (IMNM), one inclusion body myositis (IBM), 16 anti-synthetase syndrome (ASyS), four juvenile dermatomyositis (JDM), and one clinically amyopathic dermatomyositis (CADM). SD co-occurred in eight cases, including six cases of ASyS. Anti-Jo1 was observed in 13 ASyS cases and one DM. Glucocorticoids (GCSs) were administered in all patients for induction in addition to cyclophosphamide (28.6%), mycophenolate mofetil (MMF) (51.4%), and methotrexate (MTX) (17.1%). Maintenance therapy included MTX (20%), MMF (31.4%), rituximab (34.3%), azathioprine (AZA) (42.9%), and others. Two DM, two JDM, and one ASyS patient received JAK inhibitors, one DM and one JDM anifrolumab, one IBM sirolimus, and four patients with interstitial lung disease (ILD) nintedanib. Conclusions: This Polish single-centre cohort shows effective use of novel therapies for IIM. Sirolimus, JAK inhibitors, and nintedanib were effective. Co-occurrence of SD in ASyS patients requires further research. Full article

Concurrent alcohol and cannabis use (“crossfading”) is increasingly prevalent, especially among adolescents, yet its toxicological impact on pulmonary innate immunity remains largely unexplored. Alveolar macrophages (AMs) orchestrate inflammatory responses in the lung, and dysregulated macrophage polarization is a hallmark of alcohol-associated lung disease. Although alcohol and cannabinoids individually modulate immune function, the mechanisms by which their co-exposure alters macrophage activation and inflammatory signaling in the lung are largely unknown. AMs are highly sensitive to xenobiotic exposure and play a central role in regulating inflammatory and cytotoxic responses. In this study, we investigated how acute ethanol exposure, synthetic cannabinoid exposure, and their combined exposure affect macrophage viability, polarization, and the release of inflammatory mediators via cannabinoid receptor (CB1R/CB2R)-dependent pathways. Human THP-1-derived macrophages and KG-1 macrophage-like cells were exposed to ethanol, the CB1/CB2 agonist WIN 55,212-2, or both, with selective pharmacological antagonism of CB1R and CB2R. Ethanol exposure activated and polarized macrophages toward a pro-inflammatory M1 phenotype, accompanied by increased secretion of pro-inflammatory cytokines MCP-1, TGF-α, IFN-β, IL-6, and TNF-α. In contrast, WIN 55,212-2 promoted anti-inflammatory M2 polarization and increased IL-10 and IL-4 production. Notably, co-exposure to ethanol and WIN produced an antagonistic immunomodulatory response, characterized by the suppression of ethanol-induced M1 polarization and attenuation of pro-inflammatory cytokine release. Mechanistically, pharmacological CB1R blockade reduced ethanol-induced M1 polarization and cytokine secretion, whereas CB2R blockade exacerbated these effects, underscoring divergent roles for cannabinoid receptors in regulating pulmonary macrophage responses. This study provides novel findings demonstrating the mechanism by which alcohol–cannabinoid co-use reshapes macrophage immune phenotypes and identifies the endocannabinoid system as a potential therapeutic target for alcohol-related inflammatory lung disease. Full article

Tumor-associated macrophages (TAMs) are pivotal in shaping the immunosuppressive tumor microenvironment (TME). Reprogramming TAMs towards an anti-tumor M1 phenotype represents a promising strategy to enhance anti-tumor immunity. While Fe₃O₄ nanoparticles (NPs) possess immunomodulatory potential, the influence of NP size on macrophage polarization and the underlying mechanisms remain unclear. This study aims to systematically investigate the size-dependent immunomodulatory effects of Fe₃O₄ NPs and elucidate their mechanisms. We synthesized a series of Fe₃O₄ NPs of controlled sizes (5 nm, 10 nm, 30 nm, and 100 nm) via the polyol method. Among these, the 10 nm NPs demonstrated superior cellular uptake efficiency in macrophages. This enhanced uptake induced a significant increase in intracellular reactive oxygen species (ROS) levels. Subsequently, the elevated ROS activated the NF-κB signaling pathway, promoting M1 macrophage polarization. This polarization was evidenced by enhanced CD86 expression, increased nitric oxide (NO) release, and elevated secretion of pro-inflammatory cytokines. This study identifies 10 nm as the optimal size for Fe₃O₄ NPs to elicit their maximal immunomodulatory effects. Our findings establish a crucial size-design principle for the rational development of nano-immunotherapeutic agents and identify 10 nm Fe₃O₄ NPs as a promising candidate for TAM-targeted cancer therapy. Full article

Candida albicans is a yeast found in the oral cavity, gastrointestinal tract, and vaginal mucosa. This species is the most prevalent and virulent in conditions such as oral candidiasis. Myrtenol is a bicyclic monoterpene alcohol recognized for its antioxidant and anti-inflammatory attributes. Its primary source is the essential oil extracted from plants of the Myrtaceae family. This study evaluated the effect of (−)-myrtenol on the virulence factors of Candida albicans. Ten clinical isolates of Candida albicans and one reference strain (ATCC 90028) were used in this study. The virulence factors examined included adhesion, morphogenesis, and lipase production. Assays were conducted in the presence and absence of (−)-myrtenol, using a concentration corresponding to the minimum inhibitory concentration (MIC; 256 µg/mL). Results: The compound reduced the adherence of C. albicans to human oral epithelial cells (92.24 vs. 28.69), and reduced filamentation in liquid (3.17 vs. 2.57) and solid media. Furthermore, (−)-myrtenol inhibited lipase activity (0.68 vs. 1.00). Virulence factors expressed by C. albicans contribute to increased infection rates and, consequently, increased morbidity and mortality. The present findings demonstrate that (−)-myrtenol affects virulence-associated phenotypes of C. albicans in vitro. This compound represents a promising candidate for further investigation, particularly in studies addressing its mechanisms of action, safety, and potential applicability. Full article

Background/Objectives: Histone deacetylase (HDAC) inhibitors have been shown to prime the response to immunotherapy (IMT) treatment by inducing immune activation and infiltration to target tumor cells. Many studies primarily focus on adaptive immune cells and their expression of pro-inflammatory markers, like somatostatin receptor 2 (SSTR2); however, macrophages are known to help mediate key tumor microenvironment changes. The goal of this study is to evaluate the effects of HDAC inhibitors and IMT on macrophages, their expression of SSTR2, and their impact on the treatment response in triple-negative breast cancer (TNBC). Methods: Cytotoxic effects of HDAC inhibitors on 4T1 mouse mammary carcinoma cells, including suberoylanilide hydroxamic acid (SAHA), were evaluated using flow cytometry. Bone marrow-derived macrophages (BMDMs) were stimulated to M1-like and M2-like phenotypes and treated with SAHA to explore the effects on SSTR2 expression in different macrophage phenotypes. 4T1-tumor-bearing BALB/c mice were used to evaluate the therapy response to four treatments: saline control, SAHA, anti-PD-1 + anti-CTLA-4 checkpoint blockade IMT, or a combination of SAHA + IMT. Additional cohorts of 4T1-tumor-bearing BALB/c mice and NOD SCID mice, which lack adaptive immune cells, were euthanized for early evaluation of tumor-associated macrophage (TAM) populations via flow cytometry and cytokine analysis. One-way independent ANOVAs and log-rank tests were used to compare group differences. Results: SAHA promotes SSTR2 expression on M1-like BMDMs in vitro. SAHA promotes M2-like TAMs in vivo and stimulates pro-inflammatory, anti-tumor cytokine production in combination with IMT. Conclusions: SAHA drives SSTR2 expression and anti-tumor innate immune responses with additive effects in combination with immunotherapy in preclinical TNBC. Full article