White-Light Emission and Circularly Polarized Luminescence from a Chiral Copper(I) Coordination Polymer through Symmetry-Breaking Crystallization.

Achieving white-light emission, especially white circularly polarized luminescence (CPL) from a single-phase material is challenging. Herein, a pair of chiral CuI coordination polymers (1-M and 1-P) have been prepared by the asymmetrical assembly of achiral ligands and Cu2 I2 clusters. The compounds display dual emission bands and can be used as single-phase white-light phosphors, achieving a "warm"-white-light-emitting diode with an ultra-high color rendering index (CRI) of 93.4 and an appropriate correlated color temperature (CCT) of 3632 K. Meanwhile, corresponding CPL signals with maximum dissymmetry factor |glum |=8×10-3 have been observed. Hence, intrinsic white-light emission and CPL have been realized simultaneously in coordination polymers for the first time. This work gains insight into the nature of chiral assembly from achiral units and offers a prospect for the development of single-phase white-CPL materials.

Neutrophil extracellular traps enhance procoagulant activity and thrombotic tendency in patients with obstructive jaundice.

BACKGROUND & AIMS: Patients with obstructive jaundice (OJ) are considered to be prothrombotic with increased risk of thromboembolism complications. The role of neutrophil extracellular traps (NETs) in procoagulant activity (PCA) and thrombosis risk in patients with OJ is unclear. In this study, we investigated NETs formation in OJ patients and the role of elevated unconjugated bilirubin (UCB) in inducing NETs, resulting in enhanced PCA and endothelial injury. METHODS: NETs of OJ patients and healthy controls were measured. NETs PCA was assessed via coagulation time (CT), fibrin formation and purified coagulation complex production assays. Visualization of NETs and mitochondrial reactive oxygen species (MitoROS) were performed with a fluorescence microscope. We further used confocal microscopy to quantify the exposure of phosphatidylserine (PS), fibrin strands and FVa/Xa on Human umbilical vein endothelial cells (HUVECs). RESULTS: Assessment of NETs components levels revealed greater NETs production in OJ patients than in healthy controls. Importantly, OJ-NETs were responsible for enhanced PCA. UCB induced NETs formation via MitoROS accumulation and mitochondrial mobilization. HUVECs cocultured with OJ NETs lost their cell-cell junctions and consequently converted to a procoagulant phenotype. The PCA was attenuated by using DNase I alone or in combination with lactadherin. CONCLUSIONS: Our results suggest that UCB-induced NETs play a prominent role in promoting the hypercoagulable and prothrombotic state in OJ patients. The increased MitoROS accumulation in neutrophils initiated NETosis. NETs are promising targets for indicating or improving coagulation disorders in OJ patients.

Construction of a Stable Lanthanide Metal-Organic Framework as a Luminescent Probe for Rapid Naked-Eye Recognition of Fe3+ and Acetone.

Four lanthanide metal-organic frameworks (Ln-MOFs), namely {[Me2NH2][LnL]·2H2O}n (Ln = Eu 1, Tb 2, Dy 3, Gd 4), have been constructed from a new tetradentate ligand 1-(3,5-dicarboxylatobenzyl)-3,5-pyrazole dicarboxylic acid (H4L). These isostructural Ln-MOFs, crystallizing in the monoclinic P21/c space group, feature a 3D structure with 7.5 Å × 9.8 Å channels along the b axis and the point symbol of {410.614.84} {45.6}2. The framework shows high air and hydrolytic stability, which can keep stable after exposed to humid air for 30 days or immersed in water for seven days. Four MOFs with different lanthanide ions (Eu3+, Tb3+, Dy3+, and Gd3+) ions exhibit red, green, yellow, and blue emissions, respectively. The Tb-MOF emitting bright green luminescence can selectively and rapidly (<40 s) detect Fe3+ in aqueous media via a fluorescence quenching effect. The detection shows excellent anti-inference ability toward many other cations and can be easily recognized by naked eyes. In addition, it can also be utilized as a rapid fluorescent sensor to detect acetone solvent as well as acetone vapor. Similar results of sensing experiments were observed from Eu-MOF. The sensing mechanism are further discussed.

Boosting water oxidation activity by tuning the proton transfer process of cobalt phosphonates in neutral solution.

Water oxidation is a vital step in both natural and artificial photosynthetic processes. However, the effect of second coordination sphere for efficient oxygen evolution electrocatalysts has rarely been studied, becoming a bottleneck in many energy-related issues. In this article, the cobalt phosphonate (NH3C6H4NH3)Co2(hedpH)2·H2O (Co-PDA) displayed decent electrocatalytic water oxidation activity in 50 mM PBS solution (pH 7.0), comparable to the activity of state-of-the-art IrO2. Moreover, it exhibited a 160 mV lower onset potential and 6 times higher TOF than those of the counterpart, (NH4)2Co2(hedpH)2 (Co-NH4+), which existed with the same Co active center, while surrounded by different ligands. The related mechanistic studydemonstrates that the ligand in Co-PDA would benefit the proton-coupled electron transfer (PCET) processes and the formation of high valence state Co(iv).

Phosphatidylserine-exposing blood and endothelial cells contribute to the hypercoagulable state in essential thrombocythemia patients.

The mechanisms of thrombogenicity in essential thrombocythemia (ET) are complex and not well defined. Our objective was to explore whether phosphatidylserine (PS) exposure on blood cells and endothelial cells (ECs) can account for the increased thrombosis and distinct thrombotic risks among mutational subtypes in ET. Using flow cytometry and confocal microscopy, we found that the levels of PS-exposing erythrocytes, platelets, leukocytes, and serum-cultured ECs were significantly higher in each ET group [JAK2, CALR, and triple-negative (TN) (all P < 0.001)] than those in controls. Among ET patients, those with JAK2 mutations showed higher levels of PS-positive erythrocytes, platelets, neutrophils, and serum-cultured ECs than TN patients or those with CALR mutations, which show similar levels. Coagulation function assays showed that higher levels of PS-positive blood cells and serum-cultured ECs led to markedly shortened coagulation time and dramatically increased levels of FXa, thrombin, and fibrin production. This procoagulant activity could be largely blocked by addition of lactadherin (approx. 70% inhibition). Confocal microscopy showed that the FVa/FXa complex and fibrin fibrils colocalized with PS on ET serum-cultured ECs. Additionally, we found a relationship between D-dimer, prothrombin fragment F1 + 2, and PS exposure. Our study reveals a previously unrecognized link between hypercoagulability and exposed PS on cells, which might also be associated with distinct thrombotic risks among mutational subtypes in ET. Thus, blocking PS-binding sites may represent a new therapeutic target for preventing thrombosis in ET.

Phosphatidylserine on microparticles and associated cells contributes to the hypercoagulable state in diabetic kidney disease.

Background: Relatively little is known about the role of phosphatidylserine (PS) in procoagulant activity (PCA) in patients with diabetic kidney disease (DKD). This study was designed to evaluate whether exposed PS on microparticles (MPs) and MP-origin cells were involved in the hypercoagulability in DKD patients. Methods: DKD patients (n = 90) were divided into three groups based on urinary albumin excretion rate, defined as normoalbuminuria (No-A) (<30 mg/24 h), microalbuminuria (Mi-A) (30-299 mg/24 h) or macroalbuminuria (Ma-A) (>300 mg/24 h), and compared with healthy controls (n = 30). Lactadherin was used to quantify PS exposure on MPs and their original cells. Healthy blood cells (BCs) and human umbilical vein endothelial cells (HUVECs) were treated with 25, 5 or 2.5 mmol/L glucose as well as 3-12 mg/dL uric acid and cells were evaluated by clotting time and purified coagulation complex assays. Fibrin production was determined by turbidity. PS exposure and fibrin strands were observed using confocal microscopy. Results: Using flow cytometry, we found that PS+ MPs (derived from platelets, erythrocytes, HUVECs, neutrophils, monocytes and lymphocytes) and BCs were significantly higher in patients than in controls. Furthermore, the number of PS+ MPs and BCs in patients with Ma-A was significantly higher than in patients with No-A. Similarly, we observed markedly elevated PS exposure on HUVECs cultured with serum from patients with Ma-A versus serum from patients with Mi-A or normoalbuminuria. In addition, circulating PS+ MPs cooperated with PS+ cells, contributing to markedly shortened coagulation time and dramatically increased FXa/thrombin generation and fibrin formation in each DKD group. Confocal microscopy images demonstrated colocalization of fibrin with PS on HUVECs. Moreover, blockade of exposed PS on MPs and cells with lactadherin inhibited PCA by ∼80%. In vitro, BCs and endothelial cells exposed more PS in hypoglycemia or hyperglycemia. Interestingly, reconstitution experiments showed that hypoglycemia-treated cells could be further activated or injured when recovery is obtained reaching hyperglycemia. Moreover, uric acid induced PS exposure on cells (excluding platelets) at concentrations >6 mg/dL. Linear regression analysis showed that levels of PS+ BCs and microparticles were positively correlated with uric acid and proteinuria, but negatively correlated with glomerular filtration rate. Conclusions: Our results suggest that PS+ MPs and MP-origin cells play procoagulant roles in patients with DKD. Blockade of PS could become a novel therapeutic modality for the prevention of thrombosis in these patients.

Direct Solar-to-Electrochemical Energy Storage in a Functionalized Covalent Organic Framework.

A covalent organic framework integrating naphthalenediimide and triphenylamine units (NT-COF) is presented. Two-dimensional porous nanosheets are packed with a high specific surface area of 1276 m2 g-1 . Photo/electrochemical measurements reveal the ultrahigh efficient intramolecular charge transfer from the TPA to the NDI and the highly reversible electrochemical reaction in NT-COF. There is a synergetic effect in NT-COF between the reversible electrochemical reaction and intramolecular charge transfer with enhanced solar energy efficiency and an accelerated electrochemical reaction. This synergetic mechanism provides the key basis for direct solar-to-electrochemical energy conversion/storage. With the NT-COF as the cathode materials, a solar Li-ion battery is realized with decreased charge voltage (by 0.5 V), increased discharge voltage (by 0.5 V), and extra 38.7 % battery efficiency.

Polarization-independent and omnidirectional nearly perfect absorber with ultra-thin 2D subwavelength metal grating in the visible region.

A polarization-independent and omnidirectional nearly perfect absorber in the visible region has been proposed. The absorber is two-layer structure consisting of a subwavelength metal grating layer embedded in the high refractive index and lossless dielectric layer on the metal substrate. Extraordinary optical absorption with absorption peaks of over 99% can be achieved over the whole visible region for both TM and TE polarization. This absorption is attributed to cavity mode (CM) resonance caused by the coupled surface plasmon polaritons (SPP). Through adjusting the grating thickness, the absorption peak can be tuned linearly, which is highly advantageous to design various absorbers. Furthermore, the absorbance retains ultra-high over a wide angular range of incidence for both TM and TE polarization. This nearly perfect absorber offers great potential in the refractive index (RI) sensors, integrated photodetectors, solar cells and so on.

Neutrophil extracellular traps induce intrahepatic thrombotic tendency and liver damage in cholestatic liver disease.

BACKGROUND: Cholestatic liver diseases induce local and systemic hypercoagulation, with neutrophil extracellular traps (NETs) serving as major drivers. These NETs have been linked to decreased liver function in patients with obstructive jaundice. However, the impact of NETs on liver hypercoagulation in cholestatic liver disease remains unknown. METHODS: We utilized bile duct ligation to create experimental mice and analyzed NETs formation in the liver. Fibrin deposition, tissue factor expression, and inflammation in the liver were visualized through western blot and immunohistochemical techniques. LSECs were incubated with isolated NETs, and we detected endothelial procoagulant activity using coagulation protein production assays and measuring endothelial permeability. In both in vivo and in vitro settings, DNase I was applied to clarify the effect of NETs on intrahepatic hypercoagulability, hepatotoxicity, LSEC, and macrophage activation or injury. RESULTS: Bile duct ligation mice exhibited significantly increased levels of NETs in liver tissue, accompanied by neutrophil infiltration, tissue necrosis, fibrin deposition, and thrombophilia compared to sham mice. Notably, NETs resulted in phosphatidylserine and tissue factor exposure on LSEC, enhancing coagulation Factor Xa and thrombin production. The enhanced procoagulant activity could be reversed by degrading NETs with DNase I. Additionally, NETs-induced permeability changes in LSECs, characterized by increased VE-cadherin expression and F-actin retraction, which could be rescued by DNase I. Meanwhile, NET formation is associated with KC activation and the formation of inflammatory factors. CONCLUSIONS: NETs promote intrahepatic activation of coagulation and inflammation, leading to liver tissue injury. Strategies targeting NET formation may offer a potential therapeutic approach for treating cholestatic liver disease.

1D Cu(I)-based chiral organic-inorganic hybrid material with second harmonic generation and circular polarized luminescence.

In recent years, organic-inorganic hybrid materials have demonstrated exceptional performance in nonlinear optics, attracting widespread attention. However, there are relatively few examples of coordination compounds synthesized with Cu as the metal center that exhibit excellent nonlinear optical properties. In this study, we successfully synthesized a pair of enantiomers named R/S-Cu2I2 by reacting chiral ligands with CuI. The crystal structure reveals a one-dimensional copper-iodide chain structure built by Cu2I2 clusters, and its ordered arrangement in space provides not only a strong second harmonic generation (SHG) signal (1.24 × KDP) but also a large birefringence (0.15@1064 nm). Under excitation at 395 nm, the crystals exhibit red fluorescence peaked at 675 nm. The CD spectra of R/S-Cu2I2 show a distinct mirror-symmetric Cotton effect, and their CPL signals are corresponding and opposite in the emission range, with a maximum glum of approximately ±2.5 × 10-3. Theoretical calculations using density functional theory were also carried out to enhance our understanding of the correlation between their structures and optical properties.

Glycolysis inhibition induces anti-tumor central memory CD8+T cell differentiation upon combination with microwave ablation therapy.

Minimally invasive thermal therapy is a successful alternative treatment to surgery in solid tumors with high complete ablation rates, however, tumor recurrence remains a concern. Central memory CD8+ T cells (TCM) play important roles in protection from chronic infection and cancer. Here we find, by single-cell RNA analysis of human breast cancer samples, that although the memory phenotype of peripheral CD8+ T cells increases slightly after microwave ablation (MWA), the metabolism of peripheral CD8+ T cells remains unfavorable for memory phenotype. In mouse models, glycolysis inhibition by 2-deoxy-D-glucose (2DG) in combination with MWA results in long-term anti-tumor effect via enhancing differentiation of tumor-specific CD44hiCD62L+CD8+ TCM cells. Enhancement of CD8+ TCM cell differentiation determined by Stat-1, is dependent on the tumor-draining lymph nodes (TDLN) but takes place in peripheral blood, with metabolic remodeling of CD8+ T cells lasting the entire course of the the combination therapy. Importantly, in-vitro glycolysis inhibition in peripheral CD8+ T cells of patients with breast or liver tumors having been treated with MWA thrice leads to their differentiation into CD8+ TCM cells. Our work thus offers a potential strategy to avoid tumor recurrence following MWA therapy and lays down the proof-of-principle for future clinical trials.

B Cells and IL-21-Producing Follicular Helper T Cells Cooperate to Determine the Dynamic Alterations of Premetastatic Tumor Draining Lymph Nodes of Breast Cancer.

Metastasis is the major cause of cancer-related death, and lymph node is the most common site of metastasis in breast cancer. However, the alterations that happen in tumor-draining lymph nodes (TDLNs) to form a premetastatic microenvironment are largely unknown. Here, we first report the dynamic changes in size and immune status of TDLNs before metastasis in breast cancer. With the progression of tumor, the TDLN is first enlarged and immune-activated at early stage that contains specific antitumor immunity against metastasis. The TDLN is then contracted and immunosuppressed at late stage before finally getting metastasized. Mechanistically, B and follicular helper T (Tfh) cells parallelly expand and contract to determine the size of TDLN. The activation status and specific antitumor immunity of CD8+ T cells in the TDLN are determined by interleukin-21 (IL-21) produced by Tfh cells, thus showing parallel changes. The turn from activated enlargement to suppressed contraction is due to the spontaneous contraction of germinal centers mediated by follicular regulatory T cells. On the basis of the B-Tfh-IL-21-CD8+ T cell axis, we prove that targeting the axis could activate TDLNs to resist metastasis. Together, our findings identify the dynamic alterations and regulatory mechanisms of premetastatic TDLNs of breast cancer and provide new strategies to inhibit lymph node metastasis.

Preoperative single-dose camrelizumab and/or microwave ablation in women with early-stage breast cancer: A window-of-opportunity trial.

BACKGROUND: Immune checkpoint blockade has shown low response rates for advanced breast cancer, and combination strategies are needed. Microwave ablation (MWA) may be a trigger of antitumor immunity. This window-of-opportunity trial (ClinicalTrials.gov: NCT04805736) was conducted to determine the safety and feasibility of preoperative camrelizumab (an anti-PD-1 antibody) combined with MWA in the treatment of early-stage breast cancer. METHODS: Sixty participants were randomized to preoperatively receive single-dose camrelizumab alone (n = 20), MWA alone (n = 20), or camrelizumab+MWA (n = 20). A random number table was used to allocate interventions. The primary outcome was the safety and feasibility of MWA combined with camrelizumab. FINDINGS: Camrelizumab and MWA were well tolerated alone and in combination without delays in prescheduled surgery. No treatment-related grade III/IV adverse events were observed. Different from in the single-dose camrelizumab or MWA group, participants showed stable counts of blood cells after combination therapy. After combination therapy, peripheral CD8+ T cells showed enhanced cytotoxic and effect-memory functions. Clonal expansional CD8+ T cells showed higher cytotoxic activity and effector memory- and tumor-specific signatures than emergent clones after combination therapy. Enhanced interactions between clonal expansional CD8+ T cells and monocytes were observed, suggesting that monocytes contributed to the enhanced functions of clonal expansional CD8+ T cells. Major histocompatibility complex (MHC) class I-related pathways and interferon signaling pathways were activated in monocytes by combination therapy. CONCLUSIONS: Camrelizumab combined with MWA was feasible for early-stage breast cancer. Peripheral CD8+ T cells were activated after combination therapy, dependent on monocytes with activated MHC class I pathways. FUNDING: This study was supported by the Natural Science Foundation of Jiangsu Province (BK20230017).

Extraordinary optical absorption based on guided-mode resonance.

We propose a novel structure that can achieve extraordinary optical absorption over the visible spectrum, based on the guided-mode resonance effect. An optical metal grating with moderate thickness and high filling factor can lead to coupling between the quasi-guided-mode and cavity mode. The resonant interaction between the two modes can influence the field distribution, such as the magnetic field near the grating, which results in extraordinary absorption. Absorption efficiency can be optimized up to 99.16%. We also show that the absorption peak can be readily tuned just by varying the subwavelength grating period.

Typical Zollinger-Ellison syndrome-atypical location of gastrinoma and absence of hypergastrinemia: A case report and review of literature.

BACKGROUND: Zollinger-Ellison syndrome (ZES) results from hypersecretion of gastrin from pancreatic or duodenal neuroendocrine tumors, commonly referred to as gastrinomas. The high levels of gastrin lead to a typical presentation involving watery diarrhea and multiple ulcers in the duodenum. Here, we have presented the rare case of a patient with ZES and absence of hypergastrinemia as well as an atypical location of gastrinoma. CASE SUMMARY: A 72-year-old woman presented with the typical clinical manifestations of ZES, including upper abdominal pain, significant watery diarrhea, and acidic liquid vomitus. Surprisingly, however, she did not have an increased level of serum gastrin. In addition, there was no evidence of gastrinoma or any other ulcerogenic tumor. Esophagogastroduodenoscopy was conducted to examine the upper digestive tract. Revised diagnoses were considered, and an individualized treatment plan was developed. The patient responded to antacid medication while experiencing intermittent, recurring bouts of ZES. 18F-AlF-NOTA-octreotide positron emission tomography (18F-OC PET)/computed tomography (CT) helped locate the tumor. Postoperative pathology and immunohistochemistry results suggested that the tumor was a gastrinoma located at an unconventional site. CONCLUSION: This present case study demonstrates the possibility of ZES-like manifestation in patients with absence of hypergastrinemia. 18F-OC PET/CT is a relatively new imaging technique that can be applied for diagnosing even tiny gastrinomas that are atypical in terms of location.

Achieving gas pressure-dependent luminescence from an AIEgen-based metal-organic framework.

Materials exhibiting aggregation-induced emission (AIE) behaviour enable strong emission in solid state and can respond to various external stimuli, which may facilitate the development of materials for optical sensing, bioimaging or optoelectronic devices. Herein, we use an AIE luminogen 2',5'-diphenyl-[1,1':4',1"-terphenyl]-4,4"-dicarboxylic acid as the ligand to prepare an AIEgen-based MOF (metal-organic framework) named FJI-H31. FJI-H31 exhibits bright luminescence under ambient conditions (under air and at room temperature), but almost no emission is observed under vacuum. Our investigation shows that the emission intensity displays a smooth and reversible enhancement with increased gas pressure, which may be attributed to the restriction of intramolecular motion brought by structural deformation under pressure stimulus. Unlike most pressure-responsive MOFs, the luminescence reverts to its original state once gas pressure recovers. By virtue of its unique optical properties, a luminescent MOF with sensing ability of gas-pressure is realized.

Landscape of the Peripheral Immune Response Induced by Local Microwave Ablation in Patients with Breast Cancer.

Minimally invasive thermal therapies have been attempted in the treatment of breast cancer, and the immune response induced by these therapies has not been fully reported. A clinical trial is performed to determine the effect of microwave ablation (MWA) in the treatment of early-stage breast cancer. The authors perform single-cell RNA sequencing on peripheral blood mononuclear cells (PBMCs) from six patients before and after ablation. NK and CD8+ T cells are activated by MWA of breast cancer, with the increased inhibitory signature of CD8+ T cells but not dysfunctional. Enhanced co-stimulatory signature of CD4+ T cells is observed and increased frequency of ICOS+ CD4+ T cells after MWA is confirmed by flow cytometric analysis. After ablation, T-cell clones expand with increased T-cell receptor diversities. Activated antigen receptor-mediated signaling pathways are found in B cells. Enhanced interactions between B cells and CD4+ T cells are found, indicating that B cells are important antigen-presenting cells that initiate CD4+ T cells in MWA-induced immune response. Blockade of CTLA-4 or PD-1 of post-MWA PBMCs show higher T-cell activity than that of pre-MWA PBMCs. This study provide global characteristics of MWA-induced systemic immune response and pave a way for the identification of potential targets to improve the immune response.

Stepwise chemical oxidation to access ultrathin metal (oxy)-hydroxide nanosheets for the oxygen evolution reaction.

Incorporation of ultrathin nanosheets with dopants/defects shows great potential to enable metal (oxy)-hydroxide electrocatalysts with enhanced oxygen evolution reaction (OER) performance via the regulation of atomic structure and bonding arrangements. However, it remains challenging in synthesis especially for such dual control and at large scale. In this study, we present a stepwise chemical oxidation route, involving phase transition and reconstruction processes, to access ultrathin CoOOH nanosheets with a thickness of ca. 4 nm and abundant oxygen vacancies. Other transition metals were also doped into CoOOH nanosheets through this strategy. Among them, the optimized FeCoOOH nanosheets demonstrated an efficient OER activity with overpotential as low as 252 mV (current density: 10 mA cm-2) and excellent stability. A high and stable solar-to-hydrogen efficiency of 10.5% was acquired when FeCoOOH nanosheets were used as the anode in a constructed water splitting device driven by solar energy. This study offers a noble and facile strategy for potentially scalable preparation of atom-modulated ultrathin metal (oxy)-hydroxide nanosheets, and also demonstrates the OER applications.

Discontinuous moving shot technique for conformal thermal ablation in an ex vivo porcine liver model.

PURPOSE: We aimed to determine the ablation characteristics of discontinuous moving shot technique (DMST) in microwave ablation (MWA), radiofrequency ablation (RFA) and laser ablation (LA), and analyze the differences compared with fixed electrode technique (FET) in an ex vivo porcine liver model. METHODS: FET was defined as the ablation needle remaining fixed during ablation. In DMST, ablation needle moved backward for a fixed distance twice along the long axis during ablation. Four moving distances (0.5 cm, 0.75 cm, 1 cm and 2 cm) were used in DMST. Long-axis diameter (LAD) and short-axis diameter (SAD) of ablation zones were measured. The ratio of LAD/SAD was calculated. RESULTS: The shape and size of ablation zones were different between DMST and FET. Compared with FET, DMST could achieve greater LAD when the moving distance became long enough. In MWA with DMST, SAD decreased with the extension of moving distance and finally became smaller than the SAD in FET. While in LA and RFA, the change of moving distance did not affect SAD significantly. CONCLUSION: In MWA, RFA and LA, the characteristics of ablation zone of DMST were different from that of FET. This unique ablation technique may be suitable for conformal thermal ablation.

Microwave ablation of primary breast cancer inhibits metastatic progression in model mice via activation of natural killer cells.

Surgery is essential for controlling the symptoms and complications of stage IV breast cancer. However, locoregional treatment of primary tumors often results in distant progression, including lung metastasis, the most common type of visceral metastasis. As a minimally invasive thermal therapy, microwave ablation (MWA) has been attempted in the treatment of breast cancer, but the innate immune response after MWA has not yet been reported. Using two murine models of stage IV breast cancer, we found that MWA of primary breast cancer inhibited the progression of lung metastasis and improved survival. NK cells were activated after MWA of the primary tumor and exhibited enhanced cytotoxic functions, and the cytotoxic pathways of NK cells were activated. Depletion experiments showed that NK cells but not CD4+ or CD8+ T cells played a pivotal role in prolonging survival. Then, we found that compared with surgery or control treatment, MWA of the primary tumor induced completely different NK-cell-related cytokine profiles. Macrophages were activated after MWA of the primary tumor and produced IL-15 that activated NK cells to inhibit the progression of metastasis. In addition, MWA of human breast cancer stimulated an autologous NK-cell response. These results demonstrate that MWA of the primary tumor in metastatic breast cancer inhibits metastatic progression via the macrophage/IL-15/NK-cell axis. MWA of the primary tumor may be a promising treatment strategy for de novo stage IV breast cancer, although further substantiation is essential for clinical testing.