PD-1/CD80+ small extracellular vesicles from immunocytes induce cold tumours featured with enhanced adaptive immunosuppression.

Only a minority of cancer patients benefit from immune checkpoint blockade therapy. Sophisticated cross-talk among different immune checkpoint pathways as well as interaction pattern of immune checkpoint molecules carried on circulating small extracellular vesicles (sEV) might contribute to the low response rate. Here we demonstrate that PD-1 and CD80 carried on immunocyte-derived sEVs (I-sEV) induce an adaptive redistribution of PD-L1 in tumour cells. The resulting decreased cell membrane PD-L1 expression and increased sEV PD-L1 secretion into the circulation contribute to systemic immunosuppression. PD-1/CD80+ I-sEVs also induce downregulation of adhesion- and antigen presentation-related molecules on tumour cells and impaired immune cell infiltration, thereby converting tumours to an immunologically cold phenotype. Moreover, synchronous analysis of multiple checkpoint molecules, including PD-1, CD80 and PD-L1, on circulating sEVs distinguishes clinical responders from those patients who poorly respond to anti-PD-1 treatment. Altogether, our study shows that sEVs carry multiple inhibitory immune checkpoints proteins, which form a potentially targetable adaptive loop to suppress antitumour immunity.

Gradient Hydrogels Spatially Trapped Optical Cell Profiling for Quantitative Blood Cellular Osmotic Analysis.

The quantitative exploration of cellular osmotic responses and a thorough analysis of osmotic pressure-responsive cellular behaviors are poised to offer novel clinical insights into current research. This underscores a paradigm shift in the long-standing approach of colorimetric measurements triggered by red cell lysis. In this study, we engineered a purpose-driven optofluidic platform to facilitate the goal. Specifically, creating photocurable hydrogel traps surmounts a persistent challenge─optical signal interference from fluid disturbances. This achievement ensures a stable spatial phase of cells and the acquisition of optical signals for accurate osmotic response analysis at the single-cell level. Leveraging a multigradient microfluidic system, we constructed gradient osmotic hydrogel traps and developed an imaging recognition algorithm, empowering comprehensive analysis of cellular behaviors. Notably, this system has successfully and precisely analyzed individual and clustered cellular responses within the osmotic dimension. Prospective clinical testing has further substantiated its feasibility and performance in that it demonstrates an accuracy of 92% in discriminating complete hemolysis values (n = 25) and 100% in identifying initial hemolysis values (n = 25). Foreseeably, this strategy should promise to advance osmotic pressure-related cellular response analysis, benefiting further investigation and diagnosis of related blood diseases, blood quality, drug development, etc.

Transcriptomic Signature of 3D Hierarchical Porous Chip Enriched Exosomes for Early Detection and Progression Monitoring of Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is a highly lethal malignant tumor, and the current non-invasive diagnosis method based on serum markers, such as α-fetoprotein (AFP), and des-γ-carboxy-prothrombin (DCP), has limited efficacy in detecting it. Therefore, there is a critical need to develop novel biomarkers for HCC. Recent studies have highlighted the potential of exosomes as biomarkers. To enhance exosome enrichment, a silicon dioxide (SiO2) microsphere-coated three-dimensional (3D) hierarchical porous chip, named a SiO2-chip is designed. The features of the chip, including its continuous porous 3D scaffold, large surface area, and nanopores between the SiO2 microspheres, synergistically improved the exosome capture efficiency. Exosomes from both non-HCC and HCC subjects are enriched using an SiO2-chip and performed RNA sequencing to identify HCC-related long non-coding RNAs (lncRNAs) in the exosomes. This study analysis reveales that LUCAT-1 and EGFR-AS-1 are two HCC-related lncRNAs. To further detect dual lncRNAs in exosomes, quantitative real time polymerase chain reaction (qRT-PCR) is employed. The integration of dual lncRNAs with AFP and DCP significantly improves the diagnostic accuracy. Furthermore, the integration of dual lncRNAs with DCP effectively monitors the prognosis of patients with HCC and detects disease progression. In this study, a liquid biopsy-based approach for noninvasive and reliable HCC detection is developed.

Next-Generation Preclinical Functional Testing Models in Cancer Precision Medicine: CTC-Derived Organoids.

Basic and clinical cancer research requires tumor models that consistently recapitulate the characteristics of prima tumors. As ex vivo 3D cultures of patient tumor cells, patient-derived tumor organoids possess the biological properties of primary tumors and are therefore excellent preclinical models for cancer research. Patient-derived organoids can be established using primary tumor tissues, peripheral blood, pleural fluid, ascites, and other samples containing tumor cells. Circulating tumor cells acquired by non-invasive sampling feature dynamic circulation and high heterogeneity. Circulating tumor cell-derived organoids are prospective tools for the dynamic monitoring of tumor mutation evolution profiles because they reflect the heterogeneity of the original tumors to a certain extent. This review discusses the advantages and applications of patient-derived organoids. Meanwhile, this work highlights the biological functions of circulating tumor cells, the latest advancement in research of circulating tumor cell-derived organoids, and potential application and challenges of this technology.

A microfluidic hemostatic diagnostics platform: Harnessing coagulation-induced adaptive-bubble behavioral perception.

Clinical viscoelastic hemostatic assays, which have been used for decades, rely on measuring biomechanical responses to physical stimuli but face challenges related to high device and test cost, limited portability, and limited scalability.. Here, we report a differential pattern using self-induced adaptive-bubble behavioral perception to refresh it. The adaptive behaviors of bubble deformation during coagulation precisely describe the transformation of viscoelastic hemostatic properties, being free of the precise and complex physical devices. And the integrated bubble array chip allows microassays and enables multi-bubble tests with good reproducibility. Recognition of the developed bubble behaviors empowers automated and user-friendly diagnosis. In a prospective clinical study (clinical model development [n = 273]; clinical assay [n = 44]), we show that the diagnostic accuracies were 99.1% for key viscoelastic hemostatic assay indicators (reaction time [R], kinetics time [K], alpha angle [Angle], maximum amplitude [MA], lysis at 30 min [LY30]; n = 220) and 100% (n = 44) for hypercoagulation, healthy, and hypocoagulation diagnoses. This should provide fresh insight into existing paradigms and help more clinical needs.

Valve-Adjustable Optofluidic Bio-Imaging Platform for Progressive Stenosis Investigation.

The clinical evidence has proven that valvular stenosis is closely related to many vascular diseases, which attracts great academic attention to the corresponding pathological mechanisms. The investigation is expected to benefit from the further development of an in vitro model that is tunable for bio-mimicking progressive valvular stenosis and enables accurate optical recognition in complex blood flow. Here, we develop a valve-adjustable optofluidic bio-imaging recognition platform to fulfill it. Specifically, the bionic valve was designed with in situ soft membrane, and the internal air-pressure chamber could be regulated from the inside out to bio-mimic progressive valvular stenosis. The developed imaging algorithm enhances the recognition of optical details in blood flow imaging and allows for quantitative analysis. In a prospective clinical study, we examined the effect of progressive valvular stenosis on hemodynamics within the typical physiological range of veins by this way, where the inhomogeneity and local enhancement effect in the altered blood flow field were precisely described and the optical differences were quantified. The effectiveness and consistency of the results were further validated through statistical analysis. In addition, we tested it on fluorescence and noticed its good performance in fluorescent tracing of the clotting process. In virtue of theses merits, this system should be able to contribute to mechanism investigation, pharmaceutical development, and therapeutics of valvular stenosis-related diseases.

Magnetically Actuated Hydrogel Stamping-Assisted Cellular Mechanical Analyzer for Stored Blood Quality Detection.

Cellular mechanical property analysis reflecting the physiological and pathological states of cells plays a crucial role in assessing the quality of stored blood. However, its complex equipment needs, operation difficulty, and clogging issues hinder automated and rapid biomechanical testing. Here, we propose a promising biosensor assisted by magnetically actuated hydrogel stamping to fulfill it. The flexible magnetic actuator triggers the collective deformation of multiple cells in the light-cured hydrogel, and it allows for on-demand bioforce stimulation with the advantages of portability, cost-effectiveness, and simplicity of operation. The magnetically manipulated cell deformation processes are captured by the integrated miniaturized optical imaging system, and the cellular mechanical property parameters are extracted from the captured images for real-time analysis and intelligent sensing. In this work, 30 clinical blood samples with different storage durations (<14 days and >14 days) were tested. A deviation of 3.3% in the differentiation of blood storage durations by this system compared to physician annotation demonstrated its feasibility. This system should broaden the application of cellular mechanical assays in diverse clinical settings.

Space-time-regulated imaging analyzer for smart coagulation diagnosis.

The development of intelligent blood coagulation diagnoses is awaited to meet the current need for large clinical time-sensitive caseloads due to its efficient and automated diagnoses. Herein, a method is reported and validated to realize it through artificial intelligence (AI)-assisted optical clotting biophysics (OCB) properties identification. The image differential calculation is used for precise acquisition of OCB properties with elimination of initial differences, and the strategy of space-time regulation allows on-demand space time OCB properties identification and enables diverse blood function diagnoses. The integrated applications of smartphones and cloud computing offer a user-friendly automated analysis for accurate and convenient diagnoses. The prospective assays of clinical cases (n = 41) show that the system realizes 97.6%, 95.1%, and 100% accuracy for coagulation factors, fibrinogen function, and comprehensive blood coagulation diagnoses, respectively. This method should enable more low-cost and convenient diagnoses and provide a path for potential diagnostic-markers finding.

Engineered exosomes as an in situ DC-primed vaccine to boost antitumor immunity in breast cancer.

BACKGROUND: Dendritic cells (DCs) are central for the initiation and regulation of innate and adaptive immunity in the tumor microenvironment. As such, many kinds of DC-targeted vaccines have been developed to improve cancer immunotherapy in numerous clinical trials. Targeted delivery of antigens and adjuvants to DCs in vivo represents an important approach for the development of DC vaccines. However, nonspecific activation of systemic DCs and the preparation of optimal immunodominant tumor antigens still represent major challenges. METHODS: We loaded the immunogenic cell death (ICD) inducers human neutrophil elastase (ELANE) and Hiltonol (TLR3 agonist) into α-lactalbumin (α-LA)-engineered breast cancer-derived exosomes to form an in situ DC vaccine (HELA-Exos). HELA-Exos were identified by transmission electron microscopy, nanoscale flow cytometry, and Western blot analysis. The targeting, killing, and immune activation effects of HELA-Exos were evaluated in vitro. The tumor suppressor and immune-activating effects of HELA-Exos were explored in immunocompetent mice and patient-derived organoids. RESULTS: HELA-Exos possessed a profound ability to specifically induce ICD in breast cancer cells. Adequate exposure to tumor antigens and Hiltonol following HELA-Exo-induced ICD of cancer cells activated type one conventional DCs (cDC1s) in situ and cross-primed tumor-reactive CD8+ T cell responses, leading to potent tumor inhibition in a poorly immunogenic triple negative breast cancer (TNBC) mouse xenograft model and patient-derived tumor organoids. CONCLUSIONS: HELA-Exos exhibit potent antitumor activity in both a mouse model and human breast cancer organoids by promoting the activation of cDC1s in situ and thus improving the subsequent tumor-reactive CD8+ T cell responses. The strategy proposed here is promising for generating an in situ DC-primed vaccine and can be extended to various types of cancers. Scheme 1. Schematic illustration of HELA-Exos as an in situ DC-primed vaccine for breast cancer. (A) Allogenic breast cancer-derived exosomes isolated from MDA-MB-231 cells were genetically engineered to overexpress α-LA and simultaneously loaded with the ICD inducers ELANE and Hiltonol (TLR3 agonist) to generate HELA-Exos. (B) Mechanism by which HELA-Exos activate DCs in situ in a mouse xenograft model ofTNBC. HELA-Exos specifically homed to the TME and induced ICD in cancer cells, which resulted in the increased release of tumor antigens, Hiltonol, and DAMPs, as well as the uptake of dying tumor cells by cDC1s. The activated cDC1s then cross-primed tumor-reactive CD8+ T cell responses. (C) HELA-Exos activated DCs in situ in the breast cancer patient PBMC-autologous tumor organoid coculture system. ABBREVIATIONS: DCs: dendritic cells; α-LA: α-lactalbumin; HELA-Exos: Hiltonol-ELANE-α-LA-engineered exosomes; ICD: immunogenic cell death; ELANE: human neutrophil elastase; TLR3: Toll-like receptor 3; TNBC: triple-negative breast cancer; TME: tumor microenvironment; DAMPs: damage-associated molecular patterns; cDC1s: type 1 conventional dendritic cells; PBMCs: peripheral blood mononuclear cells.

Identification of a novel glycolysis-related gene signature for predicting the survival of patients with colon adenocarcinoma.

BACKGROUND: The most frequent histologic subtype of colon cancer is colon adenocarcinoma (COAD). A major problem in the diagnosis and treatment of COAD is that there is lack of new biomarkers to indicate the early stage of COAD. Compared with normally differentiated cells, the glycolytic pathways of tumor cells are more active, thus making them more adaptable to the hypoxic environment of solid tumors, which is known as the Warburg effect. Therefore, establishing a diagnostic and prognostic model based on glycolysis-related genes may provide guidance for the precise treatment of colon cancer. METHODS: The Cancer Genome Atlas (TCGA) mRNA data were used to identify differentially expressed genes (DEGs). The glycolysis-related DEGs were identified using Gene Set Enrichment Analysis (GSEA) with HALLMARK gene sets. Combined with clinical data, we identified prognostic genes in glycolysis-related DEGs based on Cox regression analysis. Four glycolysis-related genes were identified and a predictive model was developed using univariate and multivariate Cox regression analysis. cBioPortal investigated the chromosomal variations of these genes. Following that, survival analysis and receiver operating characteristic (ROC) curve validation were carried out. The correlations between glycolysis-related gene signatures and molecular features and cancer subtypes were analyzed. RESULTS: We discovered five genes (SPAG4, P4HA1, STC2, ENO3, and GPC1) that are associated with COAD patients' prognosis. The risk score was more accurate in predicting prognosis when based on this gene signature in COAD patients. Furthermore, multivariate Cox regression analysis demonstrated that the glycolysis-related gene signature's predictive value was independent of clinical variables. CONCLUSION: We identified a glycolysis-related five-gene signature and developed a risk staging model potentially valuable for the clinical management of COAD patients. Our results suggest that prognostic markers based on glycolysis-related genes may be a reliable predictive tool for the prognosis of COAD patients.

Biological Functions and Prognostic Value of Ferroptosis-Related Genes in Bladder Cancer.

Background: Every year, nearly 170,000 people die from bladder cancer worldwide. A major problem after transurethral resection of bladder tumor is that 40-80% of the tumors recur. Ferroptosis is a type of regulatory necrosis mediated by iron-catalyzed, excessive oxidation of polyunsaturated fatty acids. Increasing the sensitivity of tumor cells to ferroptosis is a potential treatment option for cancer. Establishing a diagnostic and prognostic model based on ferroptosis-related genes may provide guidance for the precise treatment of bladder cancer. Methods: We downloaded mRNA data in Bladder Cancer from The Cancer Genome Atlas and analyzed differentially expressed genes based on and extract ferroptosis-related genes. We identified relevant pathways and annotate the functions of ferroptosis-related DEGs using Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis and Gene Ontology functions. On the website of Search Tool for Retrieving Interacting Genes database (STRING), we downloaded the protein-protein interactions of DEGs, which were drawn by the Cytoscape software. Then the Cox regression analysis were performed so that the prognostic value of ferroptosis-related genes and survival time are combined to identify survival- and ferroptosis-related genes and establish a prognostic formula. Survival analysis and receiver operating characteristic curvevalidation were then performed. Risk curves and nomograms were generated for both groups to predict survival. Finally, RT-qPCR was applied to analyze gene expression. Results: Eight ferroptosis-related genes with prognostic value (ISCU, NFE2L2, MAFG, ZEB1, VDAC2, TXNIP, SCD, and JDP2) were identified. With clinical data, we established a prognostic model to provide promising diagnostic and prognostic information of bladder cancer based on the eight ferroptosis-related genes. RT-qPCR revealed the genes that were differentially expressed between normal and cancer tissues. Conclusion: This study found that the ferroptosis-related genes is associated with bladder cancer, which may serve as new target for the treatment of bladder cancer.

Touchable cell biophysics property recognition platforms enable multifunctional blood smart health care.

As a crucial biophysical property, red blood cell (RBC) deformability is pathologically altered in numerous disease states, and biochemical and structural changes occur over time in stored samples of otherwise normal RBCs. However, there is still a gap in applying it further to point-of-care blood devices due to the large external equipment (high-resolution microscope and microfluidic pump), associated operational difficulties, and professional analysis. Herein, we revolutionarily propose a smart optofluidic system to provide a differential diagnosis for blood testing via precise cell biophysics property recognition both mechanically and morphologically. Deformation of the RBC population is caused by pressing the hydrogel via an integrated mechanical transfer device. The biophysical properties of the cell population are obtained by the designed smartphone algorithm. Artificial intelligence-based modeling of cell biophysics properties related to blood diseases and quality was developed for online testing. We currently achieve 100% diagnostic accuracy for five typical clinical blood diseases (90 megaloblastic anemia, 78 myelofibrosis, 84 iron deficiency anemia, 48 thrombotic thrombocytopenic purpura, and 48 thalassemias) via real-world prospective implementation; furthermore, personalized blood quality (for transfusion in cardiac surgery) monitoring is achieved with an accuracy of 96.9%. This work suggests a potential basis for next-generation blood smart health care devices.

Strong Penetration-Induced Effective Photothermal Therapy by Exosome-Mediated Black Phosphorus Quantum Dots.

Nanocancer medicine, such as photothermal therapy (PTT), as a promising way to solve cancer without side effects, faces a huge biological barrier during the circulation of nanoparticles in the body, including nanobiological interactions in the blood, isolation of nanoparticles in the macrophage system, tumor spillover effect, and especially uneven intratumoral distribution of nanoparticles, which cast a shadow over the hope. To address the problem of intratumoral distribution, an effective photothermal agent is introduced by packaging the black phosphorus quantum dots (BPQDs) into exosome vector (EXO) through electroporation method. With the improving and proper stability for better therapy, the resulting BPQDs@EXO nanospheres (BEs) exhibit good biocompatibility, long circulation time, and excellent tumor targeting ability, hence impressive PTT efficiency evidenced by highly efficient tumor ablation in vivo. Importantly, great permeability on organoids contributed by EXO appears with BEs, which strongly promotes the efficient killing ability. These BP-based nanospheres must promise high clinical potential due to the high PTT efficiency and minimal side effects.

Circular RNAs Are Promising Biomarkers in Liquid Biopsy for the Diagnosis of Non-small Cell Lung Cancer.

The high incidence and mortality of lung cancer make early detection of lung cancer particularly important. At present, the diagnosis of lung cancer mainly depends on diagnostic imaging and tissue biopsy. However, current diagnostics are not satisfactory owing to the low specificity and inability of multiple sampling. Accumulating evidence indicates that circular RNAs (circRNAs) play a critical role in cancer progression and are promising cancer biomarkers. In particular, circRNAs are considered novel specific diagnostic markers for non-small cell lung cancer (NSCLC). Liquid biopsy is an important method in the early diagnosis of cancer due to its high sensitivity and specificity, as well as the possibility of performing multiple sampling. circRNAs are stably present in exosomes and sometimes become part of circulating nucleic acids, making them ideal for liquid biopsy. In this review, we summarize the advances in the research on circRNAs in NSCLC, and also highlight their potential applications for NSCLC detection.

Aptamer-Exosomes for Tumor Theranostics.

As carriers of biomolecules (proteins, nucleic acids, and lipids) from parent cells, exosomes play a significant role in physiology and pathology. In any diseased state, the morphology of the released exosomes remained similar. The contents of exosomes change depending on the disease or its stage; thus, exosomes are generally considered as a "source of biomarkers". Therefore, they are considered promising biomarkers for the diagnosis and prognosis of tumors. As natural delivery vehicles, exosomes can protect their cargo from immune clearance and deliver them to other cells through membrane fusion. After being genetically edited at the cell or exosome level, exosomes can be used for treatment with aptamers. Aptamers are short stretches of oligonucleotide sequences or short polypeptides that have been selected in vitro or in vivo, and have a wide range of targets and show excellent binding affinity and specificity. Aptamers have been widely used as molecular probes, and the combination of aptamers with exosomes has become a new direction for exosome-related research and therapeutic development. Here, we summarized various applications of exosomes and aptamers in cancer research, and further analyzed their combination as an "aptamer-exosome". Finally, we propose future directions for the aptamer-exosome in the precise diagnosis or personalized treatment of cancer.

COVID-19: advance in laboratory diagnostic strategy and technology.

SARS-CoV-2 is one of the beta-coronaviruses with the spike protein. It invades host cells by binding to angiotensin converting enzyme 2 (ACE2). This newly discovered virus can result in excessive inflammation and immune pathological damage, as shown by a decreased number of peripheral lymphocytes, increased levels of cytokines, and damages of lung, heart, liver, kidney, and other organs. Effective therapeutic modalities such as new antiviral drugs and vaccines against this emerging virus need to be thoroughly studied and developed. However, so far the only recognized but mild progress in this area is the screening of old drugs for new uses. Therefore, rapid and accurate laboratory SARS-CoV-2 testing approaches are the important basis of identification and blockage of COVID-19 transmission. For COVID-19 patients with different clinical classifications (mild, common, severe, and critically severe), dynamic monitoring of functional indicators of susceptible and vital organs is an important strategy for evaluating therapeutic efficacy and prognosis. In this review, we summarized SARS-CoV-2 laboratory diagnostic schemes, pathophysiological indices of tissues and organs of COVID-19 patients, and laboratory diagnostic strategies for distinct disease stages. Further, we discussed the importance of hierarchical management and dynamic observation in SARS-CoV-2 laboratory diagnostics. We then summed up the advance in SARS-CoV-2 testing technology and described the prospect of intelligent medicine in the prevention of infectious disease outbreaks.

SARS-CoV-2 vaccine research and development: Conventional vaccines and biomimetic nanotechnology strategies.

The development of a massively producible vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel coronavirus, is essential for stopping the current coronavirus disease (COVID-19) pandemic. A vaccine must stimulate effective antibody and T cell responses in vivo to induce long-term protection. Scientific researchers have been developing vaccine candidates for the severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) since the outbreaks of these diseases. The prevalence of new biotechnologies such as genetic engineering has shed light on the generation of vaccines against novel viruses. In this review, we present the status of the development of coronavirus vaccines, focusing particularly on the biomimetic nanoparticle technology platform, which is likely to have a major role in future developments of personalized medicine.

Circulating tumor cells in hepatocellular carcinoma: single-cell based analysis, preclinical models, and clinical applications.

Circulating tumor cells (CTCs) are shed into the bloodstream from primary tumors and metastatic lesions and provide significant information about tumor progression and metastasis. CTCs contribute to tumor metastasis through the epithelial-to-mesenchymal transition (EMT). CTC clusters and stem-like phenotypes lead to a more aggressive and metastatic potential. CTCs retain the heterogeneity and imitate the nature of corresponding primary tumors. Therefore, it is important to use single-cell based analysis to obtain information on tumor heterogeneity and biology. CTCs are also good candidates for building preclinical models (especially 3D organoid cultures) for drug screening, disease modeling, genome editing, tumor immunity research, and organ-like biobank establishment. In this article, we summarize the current CTC capture technology, dissect the phenotypes associated with CTC metastasis, and review the progress in single-cell based analysis and preclinical modeling of the pattern and kinetics of CTCs. In particular, we discuss the use of CTCs to assess the progression of hepatocellular carcinoma (HCC).

Co-administration of sulforaphane and doxorubicin attenuates breast cancer growth by preventing the accumulation of myeloid-derived suppressor cells.

Sulforaphane (SFN) is a compound derived from cruciferous plants shown to be effective in cancer prevention and suppression. Myeloid-derived suppressor cells (MDSCs) are known to inhibit anti-tumor immunity; however, whether SFN regulates the anti-tumor activity of MDSCs in breast cancer is still unknown. In the current study, we found that SFN blocked prostaglandin E2 (PGE2) synthesis in parental and doxorubicin (DOX)-resistant breast cancer 4T1 cell lines by activating NF-E2-related factor 2 (Nrf2). Nrf2-mediated reduction of PGE2 was dependent on the enhanced expression of heme oxygenase 1 (HO-1) and glutamate-cysteine ligase (GCLC), and decreased COX-2 expression in breast cancer cells. Moreover, our study further revealed that reduced PGE2 secretion from SFN-treated 4T1 cells triggered MDSCs to switch to an immunogenic phenotype, enhancing the anti-tumor activities of CD8+ T cells. Co-administration of SFN and DOX was more efficacious for the treatment of breast cancer in a mouse model than either agent alone, as evidenced by the significant decrease in tumor volume, MDSC expansion, and increase in cytotoxic CD8+ T cells. Taken together, our data indicate that SFN reverses the immunosuppressive microenvironment and is a potent adjuvant chemotherapeutic candidate in breast cancer.

Wilms' tumor 1 gene in hematopoietic malignancies: clinical implications and future directions.

The Wilms' tumor 1 (WT1) gene is an important regulatory molecule that plays a vital role in cell growth and development. Initially, knowledge of WT1 was mostly limited to Wilms' tumor. Over the past years, numerous studies have shown that WT1 is aberrant expressed or mutated in hematopoietic malignancies, including acute leukemia (AL), myelodysplastic syndrome (MDS) and chronic myelogenous leukemia (CML). Currently, many studies focus on exploring the role of WT1 in hematopoietic malignancies. Such studies improve the understanding of hematopoietic malignancies, and the collection of data about WT1 expression or mutation in hematopoietic malignancies over the past years can facilitate the risk stratification of hematopoietic malignancies. In this review, we highlight the important role of WT1 in hematopoietic malignancies, discuss its potential clinical applications as a minimal residual disease (MRD) and prognostic biomarker, and evaluate the possible therapy target of WT1 in hematopoietic malignancies.