siRNA Delivery against Myocardial Ischemia Reperfusion Injury Mediated by Reversibly Camouflaged Biomimetic Nanocomplexes.

siRNA-mediated management of myocardial ischemia reperfusion (IR) injury is greatly hampered by the inefficient myocardial enrichment and cardiomyocyte transfection. Herein, nanocomplexes (NCs) reversibly camouflaged with a platelet-macrophage hybrid membrane (HM) are developed to efficiently deliver Sav1 siRNA (siSav1) into cardiomyocytes, suppressing the Hippo pathway and inducing cardiomyocyte regeneration. The biomimetic BSPC@HM NCs consist of a cationic nanocore assembled from a membrane-penetrating helical polypeptide (P-Ben) and siSav1, a charge-reversal intermediate layer of poly(l-lysine)-cis-aconitic acid (PC), and an outer shell of HM. Due to HM-mediated inflammation homing and microthrombus targeting, intravenously injected BSPC@HM NCs can efficiently accumulate in the IR-injured myocardium, where the acidic inflammatory microenvironment triggers charge reversal of PC to shed off both HM and PC layers and allow the penetration of the exposed P-Ben/siSav1 NCs into cardiomyocytes. In rats and pigs, BSPC@HM NCs remarkably downregulates Sav1 in IR-injured myocardium, promotes myocardium regeneration, suppresses myocardial apoptosis, and recovers cardiac functions. This study reports a bioinspired strategy to overcome the multiple systemic barriers against myocardial siRNA delivery, and holds profound potential for gene therapy against cardiac injuries.

Short-term ex vivo tissue culture models help study human lung infectionsA review.

Most studies on human lung infection have been performed using animal models, formalin or other fixed tissues, and in vitro cultures of established cell lines. However, the experimental data and results obtained from these studies may not completely represent the complicated molecular events that take place in intact human lung tissue in vivo. The newly developed ex vivo short-term tissue culture model can mimic the in vivo microenvironment of humans and allow investigations of different cell types that closely interact with each other in intact human lung tissues. Therefore, this kind of model may be a promising tool for future studies of different human lung infections, owing to its special advantages in providing more realistic events that occur in vivo. In this review, we have summarized the preliminary applications of this novel short-term ex vivo tissue culture model, with a particular emphasis on its applications in some common human lung infections.

Macrophage-targeting gene silencing orchestrates myocardial microenvironment remodeling toward the anti-inflammatory treatment of ischemia-reperfusion (IR) injury.

Ischemia-reperfusion (IR) injury represents a major cause of myocardial dysfunction after infarction and thrombolytic therapy, and it is closely related to the free radical explosion and overwhelming inflammatory responses. Herein, macrophage-targeting nanocomplexes (NCs) are developed to mediate efficient co-delivery of siRNA against MOF (siMOF) and microRNA-21 (miR21) into myocardial macrophages, cooperatively orchestrating the myocardial microenvironment against IR injury. Bioreducible, branched poly(ß-amino ester) (BPAE-SS) is designed to co-condense siMOF and miR21 into NCs in a multivalency-reinforced approach, and they are surface-decorated with carboxylated mannan (Man-COOH) to shield the positive surface charges and enhance the serum stability. The final MBSsm NCs are efficiently internalized by myocardial macrophages after systemic administration, wherein BPAE-SS is degraded into small segments by intracellular glutathione to promote the siMOF/miR21 release, finally provoking efficient gene silencing. Thus, cardiomyocyte protection and macrophage modulation are realized via the combined effects of ROS scavenging, inflammation inhibition, and autophagy attenuation, which ameliorates the myocardial microenvironment and restores the cardiac function via positive cellular crosstalk. This study renders promising solutions to address the multiple systemic barriers against in vivo nucleic acid delivery, and it also offers new options for IR injury by manipulating multiple reciprocal bio-reactions.

POEMS syndrome causing left ventricular hypertrophy, myocardial dysfunction, and pericardial effusion: a case report.

BACKGROUND: POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, M-protein, skin changes) is a paraneoplastic syndrome caused by a plasma cell proliferative disorder. Characteristics of POEMS syndrome include elevated pro-inflammatory and angiogenic cytokine levels that lead to multi-organ dysfunction. Patients have a variety of initial symptoms, but cardiac involvement is not common. CASE SUMMARY: We report a case of a 31-year-old Chinese woman with chief complaints of chest pain and dyspnoea who was diagnosed with POEMS syndrome. The cardiovascular system in the case study patient was characterized by pericardial effusion, enlarged left atria, abnormal myocardial segmental deformation, left ventricular hypertrophy, pulmonary hypertension, and increased glucose metabolism in the left and right ventricular myocardium. The pericardial effusion diminished, while cardiac function, left ventricular wall thickness, and pulmonary hypertension gradually returned to normal with dexamethasone and bortezomib treatment. DISCUSSION: This case suggests that cardiovascular system damage may be related to systemic diseases. Cardiovascular system damage caused by POEMS syndrome is recoverable after chemotherapy treatment. Echocardiography readily visualizes the changes in the heart of a patient with POEMS syndrome, clearly reflecting the changes in the structure and function of the heart before and after treatment.

Endothelial cell-targeting, ROS-ultrasensitive drug/siRNA co-delivery nanocomplexes mitigate early-stage neutrophil recruitment for the anti-inflammatory treatment of myocardial ischemia reperfusion injury.

Neutrophils serve as a key contributor to the pathophysiology of myocardial ischemia reperfusion injury (MIRI), because the unregulated activation and infiltration of neutrophils lead to overwhelming inflammation in the myocardium to cause tissue damage. Herein, endothelial cell-targeting and  reactive oxygen species (ROS)-ultrasensitive nanocomplexes (NCs) were developed to mediate efficient co-delivery of VCAM-1 siRNA (siVCAM-1) and dexamethasone (DXM), which cooperatively inhibited neutrophil recruitment by impeding neutrophil migration and adhesion. RPPT was first synthesized via crosslinking of PEI 600 with ditellurium followed by modification with PEG and the endothelial cell-targeting peptide cRGD. RPPT was allowed to envelope the DXM-loaded PLGA nanoparticles and condense the siVCAM-1. After systemic administration in rats experiencing MIRI, the cRGD-modified NCs efficiently targeted and entered the inflamed endothelial cells, wherein RPPT was sensitively degraded by over-produced ROS to trigger intracellular siVCAM-1 release and potentiate the VCAM-1 silencing efficiency. As a consequence of the complementary function of DXM and siVCAM-1, the NCs notably mitigated neutrophil infiltration into ischemic myocardium, provoking potent anti-inflammatory efficacy to reduce MIRI and recover cardiac function. The present study offers an effective approach for the controlled co-delivery of siRNA and drug cargoes, and it also highlights the importance of multi-dimensional manipulation of neutrophils in anti-inflammatory treatment. STATEMENT OF SIGNIFICANCE: The unregulated activation and infiltration of neutrophils lead to overwhelming inflammation in the myocardium after myocardial ischemia reperfusion injury (MIRI). Here, endothelial cell-targeting and ROS-ultrasensitive nanocomplexes (NCs), comprised of PLGA NPs decorated with cRGD-poly(ethylene glycol) (PEG)-modified, ditellurium-crosslinked PEI (RPPT), were developed to mediate efficient co-delivery of VCAM-1 siRNA (siVCAM-1) and dexamethasone (DXM). DXM and siVCAM-1 with complementary functions inhibited both the migration and adhesion of neutrophils, efficiently interventing the neutrophil recruitment and interrupting the self-amplified inflammation cascade in the injured myocardium. The molecular design of RPPT renders an effective example for constructing polymeric materials with high ROS sensitivity, and it resolves the critical dilemma related to polycation-mediated siRNA delivery, such as siRNA encapsulation versus release, and transfection efficiency versus toxicity.

Curcumin is a Potential Adjuvant to Alleviates Diabetic Retinal Injury via Reducing Oxidative Stress and Maintaining Nrf2 Pathway Homeostasis.

Curcumin is a natural polyphenol compound with anti-diabetic, anti-oxidative, and anti-inflammatory effects. Although many studies have reported the protective effect of curcumin in diabetes mellitus or diabetic nephropathy, there is a lack of research on curcumin in diabetic retinopathy. The purpose of this study was to investigate the therapeutic effects of curcumin on the diabetic retinal injury. Streptozotocin (STZ)-induced diabetic rats (60, n = 12 each) were respectively given curcumin orally (200 mg/kg/day), insulin subcutaneously (4-6 IU/day), and combined therapy with curcumin and insulin for 4 weeks. Retinal histopathological changes, oxidative stress markers, and transcriptome profiles from each group were observed. Curcumin, insulin, or combination therapy significantly reduced blood glucose, alleviated oxidative stress, and improved pathological damage in diabetic rats. Curcumin not only significantly reduced retinal edema but also had a better anti-photoreceptor apoptosis effect than insulin. In the early stage of diabetes, the enhancement of oxidative stress in the retina induced the adaptive activation of the nuclear factor E2-associated factor 2 (Nrf2) pathway. Treatment of curcumin alleviated the compensatory activation of the Nrf2 pathway induced by oxidative stress, by virtue of its antioxidant ability to transfer hydrogen atoms to free radicals. When curcumin combined with insulin, the effect of maintaining Nrf2 pathway homeostasis in diabetic rats was better than that of insulin alone. Transcriptomic analyses revealed that curcumin either alone, or combined with insulin, inhibited the AGE-RAGE signaling pathway and the extracellular matrix (ECM)-receptor interaction in the diabetic retina. Thus, at the early stage of diabetes, curcumin can be used to alleviate diabetic retinal injury through its anti-oxidative effect. If taking curcumin as a potential complementary therapeutic option in combination with antihyperglycemic agents, which would lead to more effective therapeutic outcomes against diabetic complications.

[Application of Two Ultrafine Chest Tube for Drainage after
Pulmonary Uniportal Video-assisted Thoracoscopic Surgery].

BACKGROUND: At present, an ultrafine chest tube combined with a traditional thick tube were often used after pulmonary uniportal video-assisted thoracoscopic surgery (U-VATS). However, the thick tube was often placed in the incision, which increased the risk of poor wound healing and postoperative pain. The aim of this study is to investigate the feasibility and safety of using two ultrafine chest tubes (10 F pigtail tube) for drainage after pulmonary U-VATS. METHODS: The medical records of patients who underwent pulmonary U-VATS during June 2018 and June 2020 in the department of cardiothoracic surgery of the second affiliated hospital of Soochow university were retrospectively reviewed to compare two different drainage strategies, receiving two 10 F pigtail tubes as chest tube (group A) or one 10 F pigtail tube as lower chest tube combined with one 24 F tube as upper chest tube (group B). RESULTS: 106 patients in group A receiving two 10 F pigtail tubes during June 2019 and June 2020 and 183 patients in group B receiving one 10 F pigtail tube as lower chest tube combined with one 24 F tube as upper chest tube during June 2018 and June 2019 were included. There was no significant difference between two groups in terms of the postoperative thoracic drainage (mL) (1st: 199.54±126.56 vs 203.59±139.32, P=0.84; 2nd: 340.30±205.47 vs 349.74±230.92, P=0.76; 3rd: 435.19±311.51 vs 451.37±317.03, P=0.70; 4th: 492.58±377.33 vs 512.57±382.94, P=0.69; Total: 604.57±547.24 vs 614.64±546.08, P=0.88), drainage time (d) (upper chest tube: 2.54±2.20 vs 3.40±2.07, P=0.21; lower chest tube: (2.24±2.43 vs 3.82±2.12, P=0.10), postoperative hospital stays (d) (6.87±3.17 vs 7.06±3.21, P=0.63), poor wound healing (0 vs 3.28%, P=0.09), replacement of lower chest tube (0.94% vs 2.19%, P=0.66) and the VAS1 (3.00±0.24 vs 2.99±0.15, P=0.63). Notably, there were significant differences between two groups in terms of the VAS2 (2.28±0.63 vs 2.92±0.59, P<0.01) and VAS3 (2.50±1.58 vs 2.79±1.53, P=0.02), as well as the frequency of using additional analgesics (25.47% vs 38.25%, P=0.03) and replacement of the upper chest tube (0 vs 4.37%, P=0.03). CONCLUSIONS: It's feasible and safe to use two 10 F pigtail tubes for drainage after pulmonary U-VATS, which can achieve less postoperative pain and lower frequency of replacement of the upper chest tube on some specific patients.

M2 macrophage-derived exosomal long non-coding RNA AGAP2-AS1 enhances radiotherapy immunity in lung cancer by reducing microRNA-296 and elevating NOTCH2.

Long noncoding RNAs (lncRNAs) and microRNAs (miRNAs) play vital roles in human diseases. We aimed to identify the effect of the lncRNA AGAP2 antisense RNA 1 (AGAP2-AS1)/miR-296/notch homolog protein 2 (NOTCH2) axis on the progression and radioresistance of lung cancer. Expression of AGAP2-AS1, miR-296, and NOTCH2 in lung cancer cells and tissues from radiosensitive and radioresistant patients was determined, and the predictive role of AGAP2-AS1 in the prognosis of patients was identified. THP-1 cells were induced and exosomes were extracted, and the lung cancer cells were respectively treated with silenced AGAP2-AS1, exosomes, and exosomes upregulating AGAP2-AS1 or downregulating miR-296. The cells were radiated under different doses, and the biological processes of cells were assessed. Moreover, the natural killing cell-mediated cytotoxicity on lung cancer cells was determined. The relationships between AGAP2-AS1 and miR-296, and between miR-296 and NOTCH2 were verified. AGAP2-AS1 and NOTCH2 increased while miR-296 decreased in radioresistant patients and lung cancer cells. The malignant behaviors of radioresistant cells were promoted compared with the parent cells. Inhibited AGAP2-AS1, macrophage-derived exosomes, and exosomes overexpressing AGAP2-AS1 or inhibiting miR-296 facilitated the malignant phenotypes of radioresistant lung cancer cells. Furthermore, AGAP2-AS1 negatively regulated miR-296, and NOTCH2 was targeted by miR-296. M2 macrophage-derived exosomal AGAP2-AS1 enhances radiotherapy immunity in lung cancer by reducing miR-296 and elevating NOTCH2. This study may be helpful for the investigation of radiotherapy of lung cancer.

Clinical characteristics and infectivity of asymptomatic carriers of SARS-CoV-2 (Review).

Since December 2019, the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a global pandemic. At present, confirmed patients are the main source of infection, while a number of studies have indicated that asymptomatic carriers also have the ability to spread the virus. As of September 29, 2020, as the first country to report coronavirus disease 2019 (COVID-19), China has 375 asymptomatic infections according to the National Health Commission of China. Asymptomatic carriers have become the current focus of global epidemic prevention and control efforts. The present review article provides a brief introduction on the clinical characteristics and infectivity of asymptomatic carriers, and makes suggestions for the identification of asymptomatic carriers.

A narrative review of artificial intelligence-assisted histopathologic diagnosis and decision-making for non-small cell lung cancer: achievements and limitations.

OBJECTIVE: To summarize the current evidence regarding the applications, workflow, and limitations of artificial intelligence (AI) in the management of patients pathologically-diagnosed with lung cancer. BACKGROUND: Lung cancer is one of the most common cancers and the leading cause of cancer-related deaths worldwide. AI technologies have been applied to daily medical workflow and have achieved an excellent performance in predicting histopathologic subtypes, analyzing gene mutation profiles, and assisting in clinical decision-making for lung cancer treatment. More advanced deep learning for classifying pathologic images with minimal human interactions has been developed in addition to the conventional machine learning scheme. METHODS: Studies were identified by searching databases, including PubMed, EMBASE, Web of Science, and Cochrane Library, up to February 2021 without language restrictions. CONCLUSIONS: A number of studies have evaluated AI pipelines and confirmed that AI is robust and efficacious in lung cancer diagnosis and decision-making, demonstrating that AI models are a useful tool for assisting oncologists in health management. Although several limitations that pose an obstacle for the widespread use of AI schemes persist, the unceasing refinement of AI techniques is poised to overcome such problems. Thus, AI technology is a promising tool for use in diagnosing and managing lung cancer.

Characterization of Extracapsular Lymph Node Involvement and Its Clinicopathological Characteristics in Stage II-IIIA Lung Adenocarcinoma.

BACKGROUND: The prognostic impact and clinicopathological characteristics of extracapsular lymph node involvement (ECLNI) in patients with surgically resected lung adenocarcinoma (LUAD) remain unknown in the context of the eighth edition N classification. PATIENTS AND METHODS: We retrospectively reviewed 279 patients with stage II-IIIA LUAD who underwent lobectomy and lymphadenectomy. The correlations of ECLNI presence and clinicopathological profiles were analyzed. We also assessed the impact of ECLNI on the postoperative survival of pN1 and pN2 LUAD patients. RESULTS: ECLNI-positive status was more common in patients with high lymph node yield and in patients with multiple stations involved. The logistic regression model identified tumor spread through air spaces, micropapillary component, cribriform component, and nodal stage as predictive factors for ECLNI presence. LUAD patients with ECLNI presence had an increased risk of locoregional recurrence compared with those without (p < 0.001). Presence of ECLNI was confirmed as an independent risk factor for worse recurrence-free survival (RFS) (p < 0.001) and overall survival (OS) (p < 0.001) in the entire cohort. Among the 61 patients with ECLNI(+)pN2 disease, our analysis revealed that adjuvant radiation was a significant predictor of improved RFS and OS. In addition, ECLNI status provides additional precision in stratifying pN1 and pN2 patients with significantly different RFS and OS. CONCLUSIONS: Our data suggest that ECLNI remains a strong prognosticator of unfavorable OS and RFS for LUADs in the context of the eighth edition N classification. Adjuvant radiation should be actively considered for pN1b and pN2 LUAD patients with ECLNI presence.

Comparison of sublobar resection and lobectomy for patients with small (≤2cm) second primary non-small-cell lung cancer.

BACKGROUND: This study aimed to investigate whether sublobar resection (SR) is equivalent to lobectomy for small (≤ 2 cm) second primary lung cancer (SPLC). METHODS: We identified 834 patients with T1aN0M0 SPLC from the Surveillance, Epidemiology, and End Results (SEER) database during 2000-2016. Overall survival (OS) was compared between lobectomy and SR after propensity-score matching. A total of 228 patients with SPLC were identified from three institutions in China as the validation set. RESULTS: SR was an independent risk factor for patients with 1 to 2 cm SPLC (SR vs Lob: hazard ratio [HR], 1.593; 95% confidence interval [CI], 1.186-2.141; P = .002) but not for patients with SPLC ≤ 1 cm (SR vs Lob: HR, 1.206; 95% CI, 0.790-1.841; P = .385). Subgroup analysis on the SEER data indicated that OS favored lobectomy compared with SR for contralateral SPLC ≤ 2 cm but not for ipsilateral ones (ipsilateral: P = .692; contralateral: P = .030). Our multi-institutional data also revealed that SR was equivalent to lobectomy for patients with ≤2 cm ipsilateral SPLC. CONCLUSIONS: SR is equivalent to lobectomy for SPLC ≤ 1 cm but not for SPLC > 1 to 2 cm. SR might be recommended for patients with ipsilateral small SPLC considering the difficulty in reoperations.

Self-assisted membrane-penetrating helical polypeptides mediate anti-inflammatory RNAi against myocardial ischemic reperfusion (IR) injury.

Anti-inflammatory RNA interference (RNAi) provides a promising paradigm for the treatment of myocardial ischemia reperfusion (IR) injury. To overcome the membrane barriers against intracardial siRNA delivery, various guanidinated helical polypeptides with potent and aromaticity-assisted membrane activities were herein developed and used for the delivery of siRNA against RAGE (siRAGE), a critical regulator of the pro-inflammatory cascade. Aromatic modification of the polypeptide led to notably enhanced trans-membrane siRNA delivery efficiencies, and more importantly, allowed more siRNA cargoes to get internalized via non-endocytosis, an effective pathway toward gene transfection. Subsequently, benzyl-modified polypeptide (P-Ben) was identified as the top-performing material with the highest RAGE silencing efficiency yet lowest cytotoxicity in H9C2 cells. Intracardial injection of the P-Ben/siRAGE polyplexes at 150 µg siRNA per kg led to remarkable RAGE knockdown by ∼85%, thereby attenuating the inflammatory cytokine release and reducing the cardiomyocyte apoptosis as well as myocardium fibrosis to recover the cardiac function after IR injury. This study therefore provides an effective strategy for the design of membrane-penetrating gene delivery materials, and may provide a promising addition to the anti-inflammatory treatment of myocardial IR injury.

An Oncolytic Adenovirus Targeting Transforming Growth Factor ß Inhibits Protumorigenic Signals and Produces Immune Activation: A Novel Approach to Enhance Anti-PD-1 and Anti-CTLA-4 Therapy.

In an effort to develop a new therapy for cancer and to improve antiprogrammed death inhibitor-1 (anti-PD-1) and anticytotoxic T lymphocyte-associated protein (anti-CTLA-4) responses, we have created a telomerase reverse transcriptase promoter-regulated oncolytic adenovirus rAd.sT containing a soluble transforming growth factor receptor II fused with human IgG Fc fragment (sTGFßRIIFc) gene. Infection of breast and renal tumor cells with rAd.sT produced sTGFßRIIFc protein with dose-dependent cytotoxicity. In immunocompetent mouse 4T1 breast tumor model, intratumoral delivery of rAd.sT inhibited both tumor growth and lung metastases. rAd.sT downregulated the expression of several transforming growth factor ß (TGFß) target genes involved in tumor growth and metastases, inhibited Th2 cytokine expression, and induced Th1 cytokines and chemokines, and granzyme B and perforin expression. rAd.sT treatment also increased the percentage of CD8+ T lymphocytes, promoted the generation of CD4+ T memory cells, reduced regulatory T lymphocytes (Tregs), and reduced bone marrow-derived suppressor cells. Importantly, rAd.sT treatment increased the percentage of CD4+ T lymphocytes, and promoted differentiation and maturation of antigen-presenting dendritic cells in the spleen. In the immunocompetent mouse Renca renal tumor model, similar therapeutic effects and immune activation results were observed. In the 4T1 mammary tumor model, rAd.sT improved the inhibition of tumor growth and lung and liver metastases by anti-PD-1 and anti-CTLA-4 antibodies. Analysis of the human breast and kidney tumors showed that a significant number of tumor tissues expressed high levels of TGFß and TGFß-inducible genes. Therefore, rAd.sT could be a potential enhancer of anti-PD-1 and anti-CTLA-4 therapy for treating breast and kidney cancers.

[Progress in Basic Research and Clinical Treatment of Multiple Pulmonary Nodules].

Lung cancer leads to the highest cancer-related morbidity and mortality worldwide. With the development of multi-slice spiral computed tomography technology and the implement of lung cancer screening, more and more lung nodules have been discovered, many of which are multiple pulmonary nodules. These pulmonary nodules are usually diagnosed as multiple primary lung adenocarcinomas from a pathological perspective. For multiple nodules with different imaging features, the preferred treatment methods are different, and the treatment of each lung nodule is still controversial. In recent years, the interactions between multiple lesions and the evolution of the lesions as well as the inter-tumoral and intratumoral homogeneity and heterogeneity of the genomics also arouse attention. Our review gathered the research progress in multiple pulmonary nodules from the points of histopathology, genomics and surgical management.
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CD8+ Resident Memory T Cells and Viral Infection.

Tissue-resident memory T (Trm) cells are a subset of recently identified memory T cells that mainly reside and serve as sentinels in non-lymphoid peripheral tissues. Unlike the well-characterized circulating central memory T (Tcm) cells and effector memory T (Tem) cells, Trm cells persist in the tissues, do not recirculate into blood, and offer immediate protection against pathogens upon reinfection. In this review, we focus on CD8+ Trm cells and briefly introduce their characteristics, development, maintenance, and function during viral infection. We also discuss some unresolved problems, such as how CD8+ Trm cells adapt to the local tissue microenvironment, how Trm cells interact with other immune cells during their development and maintenance, and the mechanisms by which CD8+ Trm cells confer immune protection. We believe that a better understanding of these problems is of great clinical and therapeutic value and may contribute to more effective vaccination and treatments against viral infection.

Corrigendum: Expanded CURB-65: a new score system predicts severity of community-acquired pneumonia with superior efficiency.

This corrects the article DOI: 10.1038/srep22911.

A novel AXL chimeric antigen receptor endows T cells with anti-tumor effects against triple negative breast cancers.

Identifying targets for chimeric antigen receptor-modulated T lymphocyte (CAR-T) therapy against solid tumors is an urgent problem to solve. In this study, we showed for the first time that the receptor tyrosine kinase, AXL, is overexpressed in various tumor cell lines and patient tumor tissues including triple negative breast cancer (TNBC) cell lines and patient samples, making AXL a potent novel target for cancer therapy, specifically for TNBC treatment. We also engineered T cells with a CAR consisting of a novel single-chain variable fragment against AXL and revealed its antigen-specific cytotoxicity and ability to release cytokines in a TNBC cell line and other AXL-positive tumors in vitro. Furthermore, AXL-CAR-T cells displayed a significant anti-tumor effect and in vivo persistence in a TNBC xenograft model. Taken together, our findings indicate that AXL-CAR-T cells can represent a promising therapeutic strategy against TNBC.