Super High Contrast USPIO-Enhanced Cerebrovascular Angiography Using Ultrashort Time-to-Echo MRI.

Background: Ferumoxytol (Ferahame, AMAG Pharmaceuticals, Waltham, MA) is increasingly used off-label as an MR contrast agent due to its relaxivity and safety profiles. However, its potent T2∗ relaxivity limits achievable T1-weighted positive contrast and leads to artifacts in standard MRI protocols. Optimization of protocols for ferumoxytol deployment is necessary to realize its potential. Methods: We present first-in-human clinical results of the Quantitative Ultrashort Time-to-Echo Contrast Enhanced (QUTE-CE) MRA technique using the superparamagnetic iron oxide nanoparticle agent ferumoxytol for vascular imaging of the head/brain in 15 subjects at 3.0T. The QUTE-CE MRA method was implemented on a 3T scanner using a stack-of-spirals 3D Ultrashort Time-to-Echo sequence. Time-of-flight MRA and standard TE T1-weighted (T1w) images were also collected. For comparison, gadolinium-enhanced blood pool phase images were obtained retrospectively from clinical practice. Signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), and intraluminal signal heterogeneity (ISH) were assessed and compared across approaches with Welch's two-sided t-test. Results: Fifteen volunteers (54 ± 17 years old, 9 women) participated. QUTE-CE MRA provided high-contrast snapshots of the arterial and venous networks with lower intraluminal heterogeneity. QUTE-CE demonstrated significantly higher SNR (1707 ± 226), blood-tissue CNR (1447 ± 189), and lower ISH (0.091 ± 0.031) compared to ferumoxytol T1-weighted (551 ± 171; 319 ± 144; 0.186 ± 0.066, respectively) and time-of-flight (343 ± 104; 269 ± 82; 0.190 ± 0.016, respectively), with p < 0.001 in each comparison. The high CNR increased the depth of vessel visualization. Vessel lumina were captured with lower heterogeneity. Conclusion: Quantitative Ultrashort Time-to-Echo Contrast-Enhanced MR angiography provides approximately 5-fold superior contrast with fewer artifacts compared to other contrast-enhanced vascular imaging techniques using ferumoxytol or gadolinium, and to noncontrast time-of-flight MR angiography, for clinical vascular imaging. This trial is registered with NCT03266848.

The influences of AlGaN barrier epitaxy in multiple quantum wells on the optoelectrical properties of AlGaN-based deep ultra-violet light-emitting diodes.

The growth conditions of the AlGaN barrier in AlGaN/AlGaN deep ultra-violet (DUV) multiple quantum wells (MQWs) have crucial influences on the light output power of DUV light-emitting diodes (LEDs). The reduction of the AlGaN barrier growth rate improved the qualities of AlGaN/AlGaN MQWs, such as surface roughness and defects. The light output power enhancement could reach 83% when the AlGaN barrier growth rate was reduced from 900 nm h-1 to 200 nm h-1. In addition to the light output power enhancement, lowering the AlGaN barrier growth rate altered the far-field emission patterns of the DUV LEDs and increased the degree of polarization in the DUV LEDs. The enhanced transverse electric polarized emission indicates that the strain in AlGaN/AlGaN MQWs was modified by lowering the AlGaN barrier growth rate.

Population pharmacokinetic/pharmacodynamic analysis of AK111, an IL-17A monoclonal antibody, in subjects with moderate-to-severe plaque psoriasis.

AK111 is an innovative IL-17A antibody, presenting high affinity to IL-17A and showing similar pharmacokinetic (PK) characteristics to those of typical immunoglobulin (Ig) G1 antibodies. To optimize the dosage regimen for phase 2/3 clinical trials, PK and pharmacodynamics (PD) of AK111 were first characterized in Chinese moderate-to-severe plaque psoriasis patients in a phase 1b study. AK111 PK serum sample and Psoriasis Area and Severity Index (PASI) score data were collected from 48 moderate-to-severe psoriasis patients in this study. Non-linear mixed-effects modeling was used for the population PK/PD analysis. A one-compartment model with a first-order absorption and a first-order elimination best described the PK behavior of AK111. The apparent systemic clearance was 0.182 L/day, and the central volume was 6.65 L. The exposure-response relationship was characterized using an indirect response model. The pharmacological effect of AK111 was described in the form of inhibiting the formation of psoriatic plaque, whereas placebo was quantified in the form of promoting the degradation of psoriatic skin lesions. The maximum effect of drug effect (Imax) and placebo effect (PLBmax) was 1 and 0.429, respectively. The rate constant for psoriatic plaque production (Kin) was 0.474 PASI/day and psoriatic plaque loss (Kout) was 0.024 day-1. The body surface area (BSA) affected by psoriasis was identified as a significant covariate on K o u t . The simulation results confirmed that all of the predicted PASI90 response rates at week 12 were higher than 60% at 150 and 300 mg dose levels with different regimens and could reach higher than 80% at week 24. We hope this first PK/PD study of AK111 in Chinese moderate-to-severe plaque psoriasis patients will be of help in the further clinical development of AK111 and provide a reference to the dosage optimization for similar antibodies with a long half-life.

Ocular Adverse Effects in Atopic Dermatitis Patients Treated With Dupilumab: A Bibliometric Analysis.

Background: Atopic dermatitis (AD) is one of the most common chronic inflammatory skin disorders. Dupilumab, the first targeted biological drug approved for the treatment of AD, has been widely used, along with increasing ocular adverse effects (AEs). Objective: To perform a bibliometric analysis of all the qualified literature involving ocular AEs during the treatment of AD with dupilumab. Methods: Relevant studies were extracted from the Web of Science database and screened by researchers. The bibliographic analysis was performed using the VOSviewer. Results: A total of 138 articles were enrolled in this study. The first study was published in 2016 by Oregon Health and Science University from the United States. The majority of publications were published in the past 3 years. British Journal of Dermatology published the highest number of articles. The United States was the country with the most publications. Sanofi (France) and Regeneron Pharmaceuticals (USA) were the leading organizations with the most contributions. Conjunctivitis was the most common ocular AE. The management of AD will continue to be the research hotspot and development trend in this area. The milestone research is the first article "Two Phase 3 Trials of Dupilumab vs. Placebo in Atopic Dermatitis" published in the New England Journal of Medicine. Most of the top 10 papers were mainly randomized, placebo-controlled phase 2 and phase 3 clinical trials and real-life large cohort studies. Conclusions: This study may help better understand ocular AEs in the dupilumab treatment of AD, and grasp the research trends and most influential topics in this field.

Multifunctional nanocarriers of Fe3O4@PLA-PEG/curcumin for MRI, magnetic hyperthermia and drug delivery.

Background: Despite medicinal advances, cancer is still a big problem requiring better diagnostic and treatment tools. Magnetic nanoparticle (MNP)-based nanosystems for multiple-purpose applications were developed for these unmet needs. Methods: This study fabricated novel trifunctional MNPs of Fe3O4@PLA-PEG for drug release, MRI and magnetic fluid hyperthermia. Result: The MNPs provided a significant loading of curcumin (∼11%) with controllable release ability, a high specific absorption rate of 82.2 W/g and significantly increased transverse relaxivity (r2 = 364.75 mM-1 s-1). The in vivo study confirmed that the MNPs enhanced MRI contrast in tumor observation and low-field magnetic fluid hyperthermia could effectively reduce the tumor size in mice bearing sarcoma 180. Conclusion: The nanocarrier has potential for drug release, cancer treatment monitoring and therapy.

In this study, the authors designed and fabricated novel magnetic trifunctional nanoparticles of Fe₃O₄@PLA-PEG. The 8.5 nm Fe₃O₄ core was covered with the polymeric matrix of PLA-PEG to encapsulate an anticancer agent of curcumin at a content of about 11%. Curcumin release from the nanoparticles (NPs) could be controlled by applying a remote alternating magnetic field. The NPs enhanced MRI contrast, which allowed the authors to better distinguish the tumor and surroundings in MR images, which would help monitor treatment. The heat that NPs generated when applied to a field at low intensity could effectively reduce the tumor size in mice bearing sarcoma 180. The nanocarrier, therefore, has potential for cancer treatment monitoring and drug release conjuvant with magnetic hyperthermia therapy.

Do We Swallow the Waste From Our Brain?

Ferumoxytol, an iron oxide nanoparticle, was infused into the lateral cerebroventricle of awake rats to follow its movement and clearance from the brain using magnetic resonance imaging. Within minutes the contrast agent could be observed accumulating in the subarachnoid space, nasal cavity, nasal pharynx, and soft palate at the back of the throat. In a subsequent study fluorescent quantum dots were infused into the brain of rats and within 15 min could be observed in the esophagus using microscopy. These imaging studies clearly show that these large nanoparticle tracers (∼20 nm in diameter) leave the brain through the nasal cavity and end up in the gut. There are numerous studies going back decades reporting the clearance of tracers put directly into the brain. While these studies show the slow accumulation of trace in the blood and lymphatics, they report only accounting for less than 50% of what was originally put in the brain.

Association between metabolic syndrome and psoriasis: a meta-analysis of observational studies with non-psoriasis control groups.

INTRODUCTION: Psoriasis is a highly prevalent condition that affects the quality of life of affected individuals. Several studies have indicated an association between psoriasis and metabolic syndrome (MS). However, the results were inconsistent. The objective of this study was to evaluate the relationship between psoriasis and MS. MATERIAL AND METHODS: Electronic databases (PubMed, EBSCO, Elsevier, Springer, Wiley, and Cochrane) were searched systematically for published studies up to November 2, 2018. Odds ratio (OR) and 95% confidence interval (CI) were used to evaluate the association between psoriasis and MS. The heterogeneity of the study was estimated with the I2 statistic and analyzed by meta-regression and subgroup analyses. RESULTS: Twenty-two studies with a total of 137,053 participants were included in this meta-analysis. Psoriasis was associated with MS and the combined OR (95% CI) was 2.02 (1.67-2.43). The results showed high heterogeneity (I 2 = 83.60%, p < 0.001) and no publication bias among the included studies (p = 0.119). The source of controls may have influenced the heterogeneity according to the meta-regression. There was no heterogeneity in studies with matched non-psoriasis control groups according to the subgroup analysis. CONCLUSIONS: Psoriasis was associated with MS. The source of the control group was an influencing factor on heterogeneity in this study. Treating for MS in patients with psoriasis might improve psoriasis and reduce the risk of cardiovascular disease.

Mild repetitive head impacts alter perivascular flow in the midbrain dopaminergic system in awake rats.

Head injury is a known risk factor for Parkinson's disease. Disruption in the perivascular clearance of metabolic waste and unwanted proteins is thought to be a contributing factor to disease progression. We hypothesized that repetitive mild head impacts, without evidence of structural brain damage, would increase microgliosis and AQP4 expression and depolarization and alter perivascular flow in the midbrain dopaminergic system. Adult male rats were subjected to sham, or two mild head impacts separated by 48 h. Three weeks later, fully awake rats were imaged using dynamic, contrast-enhanced MRI to follow the distribution of intraventricular gadobenate dimeglumine contrast agent. Images were registered to and analysed using a 3D MRI rat atlas providing site-specific data on 171 different brain areas. Following imaging, rats were tested for cognitive function using the Barnes maze assay. Histological analyses of tyrosine hydroxylase, microglia activation and AQP4 expression and polarization were performed on a parallel cohort of head impacted rats at 20 days post insult to coordinate with the time of imaging. There was no change in the global flux of contrast agent between sham and head impacted rats. The midbrain dopaminergic system showed a significant decrease in the influx of contrast agent as compared to sham controls together with a significant increase in microgliosis, AQP4 expression and depolarization. There were no deficits in cognitive function. The histology showed a significant level of neuroinflammation in the midbrain dopaminergic system 3 weeks post mild repetitive head impact but no loss in tyrosine hydroxylase. MRI revealed no structural brain damage emphasizing the potential serious consequences of mild head impacts on sustained brain neuroinflammation in this area critical to the pathophysiology of Parkinson's.

Quantitative Imaging of Blood-Brain Barrier Permeability Following Repetitive Mild Head Impacts.

This was an exploratory study designed to evaluate the feasibility of a recently established imaging modality, quantitative ultrashort time-to-echo contrast enhanced (QUTE-CE), to follow the early pathology and vulnerability of the blood brain barrier in response to single and repetitive mild head impacts. A closed-head, momentum exchange model was used to produce three consecutive mild head impacts aimed at the forebrain separated by 24 h each. Animals were measured at baseline and within 1 h of impact. Anatomical images were collected to assess the extent of structural damage. QUTE-CE biomarkers for BBB permeability were calculated on 420,000 voxels in the brain and were registered to a bilateral 3D brain atlas providing site-specific information on 118 anatomical regions. Blood brain barrier permeability was confirmed by extravasation of labeled dextran. All head impacts occurred in the absence of any structural brain damage. A single mild head impact had measurable effects on blood brain barrier permeability and was more significant after the second and third impacts. Affected regions included the prefrontal ctx, basal ganglia, hippocampus, amygdala, and brainstem. Our findings support the concerns raised by the healthcare community regarding mild head injuries in participants in organized contact sports and military personnel in basic training and combat.

Neurovascular imaging with QUTE-CE MRI in APOE4 rats reveals early vascular abnormalities.

Cerebrovascular abnormality is linked to Alzheimer's disease and related dementias (ADRDs). ApoE-Ɛ4 (APOE4) is known to play a critical role in neurovascular dysfunction, however current medical imaging technologies are limited in quantification. This cross-sectional study tested the feasibility of a recently established imaging modality, quantitative ultra-short time-to-echo contrast-enhanced magnetic resonance imaging (QUTE-CE MRI), to identify small vessel abnormality early in development of human APOE4 knock-in female rat (TGRA8960) animal model. At 8 months, 48.3% of the brain volume was found to have significant signal increase (75/173 anatomically segmented regions; q<0.05 for multiple comparisons). Notably, vascular abnormality was detected in the tri-synaptic circuit, cerebellum, and amygdala, all of which are known to functionally decline throughout AD pathology and have implications in learning and memory. The detected abnormality quantified with QUTE-CE MRI is likely a result of hyper-vascularization, but may also be partly, or wholly, due to contributions from blood-brain-barrier leakage. Further exploration with histological validation is warranted to verify the pathological cause. Regardless, these results indicate that QUTE-CE MRI can detect neurovascular dysfunction with high sensitivity with APOE4 and may be helpful to provide new insights into health and disease.

Ferumoxytol-enhanced ultrashort TE MRA and quantitative morphometry of the human kidney vasculature.

PURPOSE: To evaluate the feasibility of Quantitative Ultrashort-Time-to-Echo Contrast-Enhanced (QUTE-CE) MRA using ferumoxytol as a contrast agent for abdominal angiography in the kidney. METHODS: Four subjects underwent ferumoxytol-enhanced MRA with the 3D UTE Spiral VIBE WIP sequence at 3 T. Image quality metrics were quantified, specifically the blood Signal-to-Noise Ratio (SNR), blood-tissue Contrast-to-Noise Ratio (CNR) and Intraluminal Signal Heterogeneity (ISH) from both the aorta and inferior vena cava (IVC). Morphometric analysis of the vessels was performed using manual approach and semi-automatic approach using Vascular Modeling ToolKit (VMTK). Image quality and branching order were compared between QUTE-CE MRA and the Gadolinium (Gd) CEMRA reference image. RESULTS: QUTE-CE MRA provides a bright blood snapshot that delineates arteries and veins equally in the same scan. The maximum SNR and CNR values were 3,282 ± 1,218 and 1,295 ± 580, respectively - significantly higher than available literature values using other CEMRA techniques. QUTE-CE MRA had lower ISH and depicted higher vessel branching order (7th vs 3rd) within the kidney compared to a standard dynamic clinical Gd CEMRA scan. Morphometric analysis yielded quantitative results for the total kidney volume, total cyst volume and for diameters of the branching arterial network down to the 7th branch. Vessel curvature was significantly increased (p < 0.001) in the presence of a renal cyst compared to equivalent vessels in normal kidney regions. CONCLUSION: QUTE-CE MRA is feasible for kidney angiography, providing greater detail of kidney vasculature, enabling quantitative morphometric analysis of the abdominal and intra-renal vessels and yielding metrics relevant to vascular diseases while using a contrast agent ferumoxytol that is safe for CKD patients.

The efficacy and safety of DermalaxTM DEEP in the correction of moderate to severe nasolabial folds: a multicenter, randomized, double-blind clinical study.

BACKGROUND: To investigate the efficacy and safety of Dermalax in the correction of moderate to severe nasolabial folds (NLFs) compared to Restylane. METHODS: A total of 324 subjects with moderate to severe NLFs were enrolled in this multicenter, randomized, double-blind, active-controlled clinical study. Eligible subjects were randomly assigned to the test group received Dermalax injection (n = 162) or control group received Restylane injection (n = 162). Clinical efficacy and safety were assessed based on the Wrinkle Severity Rating Scale (WSRS) and the Global Esthetic Improvement Scale(GAIS) at weeks 2, 8, 16, 24, 36 and 48 weeks after injection. RESULTS: At week 24, similar improvements of effective rate were obtained on the Dermalax group (93.75%) and Restylane group (89.44%). Significances were found at 36 weeks and 48 weeks after injection, Dermalax seemed be better than Restylane in maintaining the effect in the later period. The improvement of mean WSRS score for test group was superior to that of control group with significance. GAIS scores rated at week 24 were 1.65 VS 1.94 (p < .001) and 2.10 VS 2.27 (p = .060), seperately. CONCLUSIONS: Dermalax was no inferior to or better than that of the control filler Restylane in correcting of moderate to severe NLFs in Chinese subjects.

Generalized multinucleate cell angiohistiocytoma with possible origin from fibroblasts: A clinicopathological study of 15 cases.

Multinucleate cell angiohistiocytoma (MCAH) is a vascular and fibrohistiocytic proliferation with unknown pathogenesis. Clinical lesions tend to be localized to an anatomical area. Exceptionally, the generalized variant is rare. This study reports three cases of generalized MCAH, and analyzes the clinicopathological features of 15 cases reviewed in the published work. Compared with the localized variant, generalized MCAH affected both sexes equally, had an earlier age of onset and a predilection for the trunk and extremities. Histopathologically, the most characteristic feature is the giant, bizarre multinucleate cells with angulated cytoplasm. Systemic diseases or abnormal immune conditions were revealed in six patients with generalized MCAH. For the first time, we found that the present cases showed increased elastic fibers in the affected areas, suggesting that the synthetic function of fibroblasts was active. This study suggested that MCAH originates from fibroblasts and is a distinct entity with potential correlation with abnormal immune states.

DKK2 blockage-mediated immunotherapy enhances anti-angiogenic therapy of Kras mutated colorectal cancer.

There are limited options for targeted therapies for colorectal cancer (CRC). Anti-EGFR therapy is limited to CRC without KRAS mutations. Even worse, most of CRC are refractory to currently immune checkpoint blockade. DKK2, which is upregulated in CRC, was recently found to suppress host immune responses, and its blockage effectively impeded tumor progression in benign genetic CRC models in our previous study. Here, our recent study demonstrated that in human CRC tumor samples expressing high levels of DKK2, DKK2 blockade caused stronger activation of tumor infiltrating CD8+ T cells in ex vivo culture. Intriguingly, we observed a correlation of high DKK2 expression with increased lymph node metastasis prevalence in these CRC patients as well. Furthermore, in a mouse genetic CRC model with mutations in APC and KRAS, which more closely mimics advanced human CRC, we confirmed the tumor inhibitory effect of DKK2 blockade, which significantly retarded tumor progression and extended survival, with increased immune effector cell activation and reduced angiogenesis. Based on this, we performed a combined administration of DKK2 blockade with sub-optimal anti-VEGFR treatment and observed a synergetic effect on suppressing tumor angiogenesis and progression, as well as extending survival, better than those of every single therapy. Thus, this study provides further evidence for the potential therapeutic application of DKK2 blockade in the clinical treatment of human CRC.

Evaluating blood-brain barrier permeability in a rat model of type 2 diabetes.

BACKGROUND: This is an exploratory study using a novel imaging modality, quantitative ultrashort time-to-echo, contrast enhanced (QUTE-CE) magnetic resonance imaging to evaluate the permeability of the blood-brain barrier in a rat model of type 2 diabetes with the presumption that small vessel disease is a contributing factor to neuropathology in diabetes. METHODS: The BBZDR/Wor rat, a model of type 2 diabetes, and age-matched controls were studied for changes in blood-brain barrier permeability. QUTE-CE, a quantitative vascular biomarker, generated angiographic images with over 500,000 voxels that were registered to a 3D MRI rat brain atlas providing site-specific information on blood-brain barrier permeability in 173 different brain areas. RESULTS: In this model of diabetes, without the support of insulin treatment, there was global capillary pathology with over 84% of the brain showing a significant increase in blood-brain barrier permeability over wild-type controls. Areas of the cerebellum and midbrain dopaminergic system were not significantly affected. CONCLUSION: Small vessel disease as assessed by permeability in the blood-brain barrier in type 2 diabetes is pervasive and includes much of the brain. The increase in blood-brain barrier permeability is a likely contributing factor to diabetic encephalopathy and dementia.

Imaging the effect of the circadian light-dark cycle on the glymphatic system in awake rats.

The glymphatic system functions in the removal of potentially harmful metabolites and proteins from the brain. Dynamic, contrast-enhanced MRI was used in fully awake rats to follow the redistribution of intraventricular contrast agent entrained to the light-dark cycle and its hypothetical relationship to the sleep-waking cycle, blood flow, and brain temperature in specific brain areas. Brain areas involved in circadian timing and sleep-wake rhythms showed the lowest redistribution of contrast agent during the light phase or time of inactivity and sleep in rats. Global brain redistribution of contrast agent was heterogeneous. The redistribution was highest along the dorsal cerebrum and lowest in the midbrain/pons and along the ventral surface of the brain. This heterogeneous redistribution of contrast agent paralleled the gradients and regional variations in brain temperatures reported in the literature for awake animals. Three-dimensional quantitative ultrashort time-to-echo contrast-enhanced imaging was used to reconstruct small, medium, and large arteries and veins in the rat brain and revealed areas of lowest redistribution overlapped with this macrovasculature. This study raises new questions and theoretical considerations of the impact of the light-dark cycle, brain temperature, and blood flow on the function of the glymphatic system.

HSP90 regulates osteosarcoma cell apoptosis by targeting the p53/TCF-1-mediated transcriptional network.

Osteosarcoma (OS) is the most common bone tumor that occurs predominantly in children and teenagers. Although many genes, such as p53 and Rb1, have been shown to be mutated, deregulation of the canonical Wnt/ß-catenin signaling pathway is frequently observed in OS. We recently demonstrated that heat shock protein 90 (HSP90) is involved in the regulation of runt-related transcription factor 2 via the AKT/GSK-3ß/ß-catenin signaling pathway in OS. However, the precise role of T cell factors/lymphoid enhancer-binding factor (TCFs/LEF) family members, which are the major binding complex of ß-catenin, in OS is poorly understood. In the present study, we first demonstrated that TCF-1 is overexpressed in OS compared with other bone tumors. Knockdown of TCF-1 significantly induced cell cycle arrest, severe DNA damage, and subsequent caspase-3-dependent apoptosis. Interestingly, coexpression of HSP90 and TCF-1 was observed in OS, and mechanistically, we demonstrated that TCF-1 expression is regulated by HSP90 either through a ß-catenin-dependent mechanism or a direct degradation of the proteasome. We also found that overexpression of TCF-1 partially abolishes the apoptosis induced by HSP90 inhibition. Furthermore, we provided evidence that p53, but not miR-34a, plays a crucial role in the HSP90-regulated TCF-1 expression and subsequent apoptosis. Given the diverse combination regimens of HSP90 inhibition with some other treatments, we propose that the p53 status and the expression level of TCF-1 should be taken into consideration to enhance the therapeutic efficacy of HSP90 inhibition.

Data on MRI brain lesion segmentation using K-means and Gaussian Mixture Model-Expectation Maximization.

The data in this article provide details about MRI lesion segmentation using K-means and Gaussian Mixture Model-Expectation Maximization (GMM-EM) algorithms. Both K-means and GMM-EM algorithms can segment lesion area from the rest of brain MRI automatically. The performance metrics (accuracy, sensitivity, specificity, false positive rate, misclassification rate) were estimated for the algorithms and there was no significant difference between K-means and GMM-EM. In addition, lesion size does not affect the accuracy and sensitivity for either method.

Neutralizing monoclonal antibody against Dickkopf2 impairs lung cancer progression via activating NK cells.

Adenomatous polyposis coli (APC) and KRAS proto-oncogene (KRAS) mutations frequently co-occur in non-small cell lung cancer. Inactivating APC mutations in colorectal carcinoma has been well characterized, leading to the approaches targeting on dysregulated APC pathway. However, it remains undetermined whether such approaches are also applicable to non-small cell lung cancer patients harboring similar mutations of APC. Dickkopf-related protein 2 (DKK2) is a Wnt antagonist. Our previous study has proved that anti-DKK2 antibody 5F8 suppressed the growth of colorectal carcinoma with APC mutations, illustrating a new target agent of APC-mutated tumors. This study aimed to investigate the potential of applying anti-DKK2 antibody to non-small cell lung cancer with APC mutations. We found significant upregulation of Dkk2 expression in APC-mutated lung cancers. Administration of DKK2 antibody inhibited cancer growth via modulating tumor immune microenvironment in lung cancer mouse models. Our study provided strong evidence supporting APC mutations-directed applications of anti-DKK2 targeted therapy in a wide range of cancer types, including lung cancer.