A system of repressor gradients spatially organizes the boundaries of Bicoid-dependent target genes.

The homeodomain (HD) protein Bicoid (Bcd) is thought to function as a gradient morphogen that positions boundaries of target genes via threshold-dependent activation mechanisms. Here, we analyze 66 Bcd-dependent regulatory elements and show that their boundaries are positioned primarily by repressive gradients that antagonize Bcd-mediated activation. A major repressor is the pair-rule protein Runt (Run), which is expressed in an opposing gradient and is necessary and sufficient for limiting Bcd-dependent activation. Evidence is presented that Run functions with the maternal repressor Capicua and the gap protein Kruppel as the principal components of a repression system that correctly orders boundaries throughout the anterior half of the embryo. These results put conceptual limits on the Bcd morphogen hypothesis and demonstrate how the Bcd gradient functions within the gene network that patterns the embryo.

Multiplexed bioluminescence microscopy via phasor analysis.

Bioluminescence imaging with luciferase-luciferin pairs is a well-established technique for visualizing biological processes across tissues and whole organisms. Applications at the microscale, by contrast, have been hindered by a lack of detection platforms and easily resolved probes. We addressed this limitation by combining bioluminescence with phasor analysis, a method commonly used to distinguish spectrally similar fluorophores. We built a camera-based microscope equipped with special optical filters to directly assign phasor locations to unique luciferase-luciferin pairs. Six bioluminescent reporters were easily resolved in live cells, and the readouts were quantitative and instantaneous. Multiplexed imaging was also performed over extended time periods. Bioluminescent phasor further provided direct measures of resonance energy transfer in single cells, setting the stage for dynamic measures of cellular and molecular features. The merger of bioluminescence with phasor analysis fills a long-standing void in imaging capabilities, and will bolster future efforts to visualize biological events in real time and over multiple length scales.

Transplantation of A2 type astrocytes promotes neural repair and remyelination after spinal cord injury.

BACKGROUND: Limited progress in terms of an effective treatment for spinal cord injury (SCI) emphasizes the urgent need for novel therapies. As a vital central nervous system component, the resident astrocytes play crucial roles in regulating recovery after SCI. In this study, recovery after SCI was compared following the transplantation of either A1 or A2 astrocytes. A1 astrocytes are harmful as they upregulate the neurotoxic classical complement cascade genes. Conversely, A2 astrocytes are characterized as neuroprotective as they upregulate the production of many neurotrophic factors. METHODS: We used different supernatant obtained from microglia stimulated with lipopolysaccharide or interleukin-4 to generate A1 and A2 astrocytes. We detected the influence of astrocytes on neurons by co-culturing A1 and A2 astrocytes with neurons. We transplanted astrocytes into the lesion site of the spinal cord and assessed lesion progression, neural restoration, glia formation and locomotor recovery. RESULTS: Astrocytes were polarized into A1 and A2 phenotypes following culture in the supernatant obtained from microglia stimulated with lipopolysaccharide or interleukin-4, respectively. Furthermore, co-culturing A2 astrocytes with neurons significantly suppressed glutamate-induced neuronal apoptosis and promoted the degree of neuron arborization. Transplantation of these A2 astrocytes into the lesion site of the spinal cord of mice significantly improved motor function recovery, preserved spared supraspinal pathways, decreased glia scar deposition, and increased neurofilament formation at the site of injury compared to the transplantation of A1 astrocytes. Additionally, enhanced A2 astrocytes with potentially beneficial A2-like genes were also detected in the A2 group. Moreover, luxol fast blue staining and electron microscopy indicated increased preservation of myelin with organized structure after transplantation of A2 astrocytes than of A1 astrocytes. CONCLUSIONS: A2 astrocyte transplantation could be a promising potential therapy for SCI. Video abstract.

Targeting the KRT16-vimentin axis for metastasis in lung cancer.

Lung cancer is the most diagnosed malignant cancer and the leading cause of cancer-related deaths worldwide, with advanced stage and metastasis being a major issue. The mechanism leading to metastasis is not yet understood. Here, we found that KRT16 is upregulated in metastatic lung cancer tissues and correlated with poor overall survival. Knockdown of KRT16 inhibits metastasis of lung cancer both in vitro and in vivo. Mechanistically, KRT16 interacts with vimentin, and depletion of KRT16 leads to downregulation of vimentin. KRT16 acquired its oncogenic ability by stabilizing vimentin, and vimentin is required for KRT16-driven metastasis. FBXO21 mediates the polyubiquitination and degradation of KRT16, and vimentin inhibits KRT16 ubiquitination and degradation by impairing its interaction with FBXO21. Significantly, IL-15 inhibits metastasis of lung cancer in a mouse model through upregulation of FBXO21, and the level of IL-15 in circulating serum was significantly higher in nonmetastatic lung cancer patients than in metastatic patients. Our findings indicate that targeting the FBXO21/KRT16/vimentin axis may benefit lung cancer patients with metastasis.

Active Breathing Coordinator reduces radiation dose to the stomach in patients with left breast cancer.

BACKGROUND/PURPOSE: Gastric dose parameters comparison for deep inspiration breath-hold (DIBH) or free breathing (FB) mode during radiotherapy (RT) for left-sided breast cancer patients (LSBCPs) has not been investigated before. This study aimed to analyze the impact of Active Breath Coordinator (ABC)-DIBH technique on the dose received by the stomach during RT for LSBCPs and to provide organ-specific dosimetric parameters. MATERIALS AND METHODS: The study included 73 LSBCPs. The dosimetric parameters of the stomach were compared between FB and DIBH mode. The correlation between the stomach volume and dosimetric parameters was analyzed. RESULTS: Compared to FB mode, statistically significant reductions were observed in gastric dose parameters in ABC-DIBH mode, including Dmax (46.60 vs 17.25, p < 0.001), D1cc (38.42 vs 9.60, p < 0.001), Dmean (4.10 vs 0.80, p < 0.001), V40Gy (0.50 vs 0.00, p < 0.001), V30Gy (6.30 vs 0.00, p < 0.001), V20Gy (20.80 vs 0.00, p < 0.001), V10Gy (51.10 vs 0.77, p < 0.001), and V5Gy (93.20 vs 9.60, p < 0.001). ABC-DIBH increased the distance between the stomach and the breast PTV when compared to FB, from 1.3 cm to 2.8 cm (p < 0.001). Physiologic decrease in stomach volume was not found from FB to ABC-DIBH (415.54 cm3 vs 411.61 cm3, p = 0.260). The stomach volume showed a positive correlation with V40Gy (r2 = 0.289; p < 0.05), V30Gy (r2 = 0.287; p < 0.05), V20Gy (r2 = 0.343; p < 0.05), V10Gy (r2 = 0.039; p < 0.001), V5Gy (r2 = 0.439; p < 0.001), Dmax (r2 = 0.269; p < 0.05) and D1cc (r2 = 0.278; p < 0.05) in FB mode. While in ABC-DIBH mode, most stomach dosimetric parameters were not correlated with gastric volume. CONCLUSIONS: The implementation of ABC-DIBH in LSBCPs radiotherapy resulted in lower irradiation of the stomach. Larger stomach volume was associated with statistically significantly higher dose irradiation in FB mode. To reduce radiotherapy related side effects in FB mode, patients should be fast for at least 2 hours before the CT simulation and treatment.

Visualization of the process of a nanocarrier-mediated gene delivery: stabilization, endocytosis and endosomal escape of genes for intracellular spreading.

Nanoparticles have been widely applied as gene carrier for improving RNA interference (RNAi) efficiency in medical and agricultural fields. However, the mechanism and delivery process of nanoparticle-mediated RNAi is not directly visualized and elucidated. Here we synthesized a star polymer (SPc) consisted of a hydrophilic shell with positively-charged tertiary amine in the side chain, which was taken as an example to investigate the mechanism in gene delivery. The SPc could assemble with dsRNA spontaneously through electrostatic force, hydrogen bond and van der Waals force. Interestingly, the SPc could protect dsRNA from degradation by RNase A and insect hemolymph, thus remarkably increasing the stability of dsRNA. Meanwhile, the SPc could efficiently promote the cellular uptake and endosomal escape for intracellular spreading of dsRNA. Transcriptome analysis revealed that the SPc could up-regulate some key genes such as Chc, AP2S1 and Arf1 for activating clathrin-mediated endocytosis. Furthermore, the suppression of endocytosis hindered the cellular uptake of SPc-delivered dsRNA in vitro, and the subsequent RNAi effect was also disappeared in vivo. To our knowledge, our study is the first direct visualization of the detailed cellular delivery process and mechanism of nanocarrier-mediated gene delivery. Above mechanism supports the application of nanocarrier-based RNAi in gene therapy and pest management.

Impacts of the ubiquitous factor Zelda on Bicoid-dependent DNA binding and transcription in Drosophila.

In vivo cross-linking studies suggest that the Drosophila transcription factor Bicoid (Bcd) binds to several thousand sites during early embryogenesis, but it is not clear how many of these binding events are functionally important. In contrast, reporter gene studies have identified >60 Bcd-dependent enhancers, all of which contain clusters of the consensus binding sequence TAATCC. These studies also identified clusters of TAATCC motifs (inactive fragments) that failed to drive Bcd-dependent activation. In general, active fragments showed higher levels of Bcd binding in vivo and were enriched in predicted binding sites for the ubiquitous maternal protein Zelda (Zld). Here we tested the role of Zld in Bcd-mediated binding and transcription. Removal of Zld function and mutations in Zld sites caused significant reductions in Bcd binding to known enhancers and variable effects on the activation and spatial positioning of Bcd-dependent expression patterns. Also, insertion of Zld sites converted one of six inactive fragments into a Bcd-responsive enhancer. Genome-wide binding experiments in zld mutants showed variable effects on Bcd-binding peaks, ranging from strong reductions to significantly enhanced levels of binding. Increases in Bcd binding caused the precocious Bcd-dependent activation of genes that are normally not expressed in early embryos, suggesting that Zld controls the genome-wide binding profile of Bcd at the qualitative level and is critical for selecting target genes for activation in the early embryo. These results underscore the importance of combinatorial binding in enhancer function and provide data that will help predict regulatory activities based on DNA sequence.

Characterization of a Plasmid-Encoded Resistance-Nodulation-Division Efflux Pump in Klebsiella pneumoniae and Klebsiella quasipneumoniae from Patients in China.

Two multidrug-resistant (MDR) mcr-1-harboring Klebsiella pneumoniae isolates from patients with urinary tract infections and one MDR Klebsiella quasipneumoniae isolate from a patient with bloodstream infection were identified to carry tmexCD1-toprJ1 The addition of the efflux pump inhibitor reduced the tigecycline MIC against all three isolates by 8- to 16-fold. pKQBSI104-1 was transferred from K. quasipneumoniae to Escherichia coli J53 via conjugation. The tmexCD1-toprJ1-carrying plasmids pKP15ZE495-1 (102,569 bp) and pKQBSI104-1 (121,996 bp) were completely sequenced and analyzed.

Publisher Correction: Precision and accuracy of single-molecule FRET measurements-a multi-laboratory benchmark study.

This paper was originally published under standard Springer Nature copyright. As of the date of this correction, the Analysis is available online as an open-access paper with a CC-BY license. No other part of the paper has been changed.

Precision and accuracy of single-molecule FRET measurements-a multi-laboratory benchmark study.

Single-molecule Förster resonance energy transfer (smFRET) is increasingly being used to determine distances, structures, and dynamics of biomolecules in vitro and in vivo. However, generalized protocols and FRET standards to ensure the reproducibility and accuracy of measurements of FRET efficiencies are currently lacking. Here we report the results of a comparative blind study in which 20 labs determined the FRET efficiencies (E) of several dye-labeled DNA duplexes. Using a unified, straightforward method, we obtained FRET efficiencies with s.d. between ±0.02 and ±0.05. We suggest experimental and computational procedures for converting FRET efficiencies into accurate distances, and discuss potential uncertainties in the experiment and the modeling. Our quantitative assessment of the reproducibility of intensity-based smFRET measurements and a unified correction procedure represents an important step toward the validation of distance networks, with the ultimate aim of achieving reliable structural models of biomolecular systems by smFRET-based hybrid methods.

Downregulation of FPR1 abates lipopolysaccharide-induced inflammatory injury and apoptosis by upregulating MAPK signaling pathway in murine chondrogenic ATDC5 cells.

BACKGROUND AND OBJECTIVE: Osteoarthritis is the most common chronic osteoarthrosis disease. There are complex factors that lead to osteoarthritis. Therefore, it is essential to investigate the molecular mechanism of osteoarthritis, especially the mechanism of articular cartilage degeneration. In this study, the mechanism of FPR1 (formyl peptide receptor 1) in LPS (lipopolysaccharide) induced chondrogenic cell ATDC5 was investigated. MATERIALS AND METHODS: We employed real-time quantitative polymerase chain reaction (RT-qPCR) and western blot assay to analyze the expression level of FPR1 in ATDC5 cell lines induced by LPS at 0, 2.5, 5, and 10 µg/mL concentrations. Then we constructed the FPR1 knockdown plasmid to transfect the LPS-ATDC5. MTT assay was used to test cell viability in control, LPS, LPS+shNC and LPS+shFPR1 groups. ELISA and RT-qPCR assay were employed to examine the TNF-α (tumor necrosis factor-α)Í¿IL-6 and IL-1ß expression level. Flow cytometry and western blot assay were employed to analyze the apoptosis of LPS-ATDC5. Finally, we utilized the western blot assay to text related protein expression level of MAPK (mitogen-activated protein kinase) signaling pathway. RESULTS: In this study, we found the expression level of FPR1 was increased in LPS-ATDC5, downregulation of FPR1 improves the survival rate and alleviates inflammatory response of LPS-ATDC5. Meanwhile, downregulation of FPR1 alleviates apoptosis of LPS-ATDC5. Finally, downregulation of FPR1 inhibits the MAPK signal pathway. CONCLUSION: Present study revealed that FPR1 was highly expressed in LPS-induced chondrocytes ATDC5, and the downregulation of FPR1 abated the inflammatory response and apoptosis of LPS-ATDC5 cells by regulating the MAPK signaling pathway.

Auxiliary Diagnosis for COVID-19 with Deep Transfer Learning.

To assist physicians identify COVID-19 and its manifestations through the automatic COVID-19 recognition and classification in chest CT images with deep transfer learning. In this retrospective study, the used chest CT image dataset covered 422 subjects, including 72 confirmed COVID-19 subjects (260 studies, 30,171 images), 252 other pneumonia subjects (252 studies, 26,534 images) that contained 158 viral pneumonia subjects and 94 pulmonary tuberculosis subjects, and 98 normal subjects (98 studies, 29,838 images). In the experiment, subjects were split into training (70%), validation (15%) and testing (15%) sets. We utilized the convolutional blocks of ResNets pretrained on the public social image collections and modified the top fully connected layer to suit our task (the COVID-19 recognition). In addition, we tested the proposed method on a finegrained classification task; that is, the images of COVID-19 were further split into 3 main manifestations (ground-glass opacity with 12,924 images, consolidation with 7418 images and fibrotic streaks with 7338 images). Similarly, the data partitioning strategy of 70%-15%-15% was adopted. The best performance obtained by the pretrained ResNet50 model is 94.87% sensitivity, 88.46% specificity, 91.21% accuracy for COVID-19 versus all other groups, and an overall accuracy of 89.01% for the three-category classification in the testing set. Consistent performance was observed from the COVID-19 manifestation classification task on images basis, where the best overall accuracy of 94.08% and AUC of 0.993 were obtained by the pretrained ResNet18 (P < 0.05). All the proposed models have achieved much satisfying performance and were thus very promising in both the practical application and statistics. Transfer learning is worth for exploring to be applied in recognition and classification of COVID-19 on CT images with limited training data. It not only achieved higher sensitivity (COVID-19 vs the rest) but also took far less time than radiologists, which is expected to give the auxiliary diagnosis and reduce the workload for the radiologists.

Emerging role of lncRNAs in renal fibrosis.

Fibrosis is the final common pathological feature of a wide variety of chronic kidney disease (CKD). However, an understanding of the mechanisms underlying the development of renal fibrosis remains challenging and controversial. As the current focus of molecular research, noncoding RNAs (ncRNAs), mainly microRNAs (miRNAs), long noncoding RNAs (lncRNAs) and circular noncoding RNAs (circRNAs), have powerful and abundant biological functions, which essentially makes them mediators of the physiological and pathological processes of various system diseases. The role of ncRNAs in renal fibrosis has also received great attention in recent years, but most research has mainly focused on miRNAs. In fact, although a large number of studies of lncRNAs have emerged recently, the role these molecules play in renal fibrosis haven't been fully understood till now. Thus, this review discusses the discovery of lncRNAs and their biological functions in different types of renal fibrosis, as well as the imminent applications of these findings in clinical use. Undoubtedly, in the future, further understanding of the function of all types of lncRNAs will reveal large breakthroughs in the treatment of renal fibrosis.

Excess administration of miR-340-5p ameliorates spinal cord injury-induced neuroinflammation and apoptosis by modulating the P38-MAPK signaling pathway.

Spinal cord injury (SCI) is a destructive polyneuropathy that can result in loss of sensorimotor function and sphincter dysfunction, and even death in critical situations. MicroRNAs (miRs) are a series of non-coding RNA molecules that are involved in transcriptional regulation. Previous studies have demonstrated that modulation of multiple miRs is involved in neurological recovery after SCI. However, the functions of miR-340-5p in SCI remain uncertain. Therefore, we probed the therapeutic effect and mechanism of miR-340-5p in microglia in vitro and in vivo in SCI rats. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blotting were employed to examine the alterations in miR-340-5p and P38 levels in SCI rats. miR-340-5p targets in microglia were ascertained using luciferase reporter assays, immunofluorescence analyses, and western blotting. We also established an SCI model and administered miR-340-5p. The effects of miR-340-5p on the amelioration of inflammation, oxidative stress, and apoptosis following SCI were assessed using immunofluorescence, immunohistochemistry, and histological analyses. Finally, locomotor function recovery was determined using the Basso, Beattie, Bresnahan rating scale. In our study, the expression profiles and luciferase assay results clarified that P38 was a target of miR-340-5p, which was associated with activation of the P38-MAPK signaling pathway. Elevation of miR-340-5p decreased P38 expression, subsequently inhibiting the inflammatory reaction. SCI-induced secondary neuroinflammation was relieved under miR-340-5p treatment. Moreover, by controlling neuroinflammation, the increased levels of miR-340-5p might counter oxidative stress and reduce the degree of apoptosis. We also observed decreasing gliosis and glial scar formation and increasing neurotrophin expression at the chronic stage of SCI. Together, these potential effects of miR-340-5p treatment ultimately improved locomotor function recovery in SCI rats.

Ag-Sn bimetallic nanoparticles paste for high temperature service in power devices.

In this paper, high strength Cu-Cu interconnections were achieved by sintering the paste of Ag-Sn bimetallic nanoparticles at low temperature. Compared with nano-Ag paste, the outer Sn coatings of the nano-Ag particles were found to be favorable for the densification of the bondline. The microstructures of Ag-Sn bimetallic nanoparticles and the bondlines under different sintereing conditions were studied in detail by x-ray photoelectron spectroscopy (XPS), x-ray diffraction (XRD), scanning electron microscopy (SEM), and transmission electron microscopy (TEM). The Ag-Sn bimetallic nanoparticles bondline exhibit a high shear strength of 35.3 MPa and a low resistivity of 9.5 µΩ cm, when sintered at 260 °C for 20 min under a pressure of 0.5 MPa. The electrochemical migration time of this sintered Ag-Sn bimetallic nanoparticles was prolonged to be ten times of that of sintered nano-Ag. This bonding technology based on Ag-Sn bimetallic nanoparticles was a promising die attach method for high temperature power device packaging.

Emerging role of miRNAs in renal fibrosis.

As one type of the most common endogenous short noncoding RNAs (ncRNAs), microRNAs (miRNAs) act as posttranscriptional regulators of gene expression and have great potential biological functions in the physiological and pathological processes of various diseases. The role of miRNAs in renal fibrosis has also attracted great attention in the previous 20 years, and new therapeutic strategies targeting miRNAs appear to be promising. Some researchers have previously reviewed the roles of miRNA in renal fibrosis disease, but numerous studies have emerged over the recent 5 years. It is necessary to update and summarize research progress in miRNAs in renal fibrosis. Thus, in this review, we summarize progress in miRNA-mediated renal fibrosis over the last 5 years and evaluate the biological functions of some miRNAs in different stages of renal fibrosis. Furthermore, we also expound the recent clinical applications of these miRNAs to provide new insights into the treatment of renal fibrosis disease.

Rapid Fulminant Progression and Mortality Secondary to Aeromonas dhakensis Septicemia with Hepatitis B Virus Infection Following the Ingestion of Snakehead Fish in Mainland China: A Case Report.

Aeromonas dhakensis is an important ubiquitous Gram-negative and freshwater bacterium detected in different reservoirs. It can cause invasive diseases in humans. Herein, we report the first case in Mainland China of a fulminant death of a 29-year-old man as a result of a new, unexpected association between septicemic A. dhakensis and hepatitis B viral infection (HBV). Herein, the patient died from multiple organ failure 5 d postadmission after the ingestion of Snakehead Fish meal. The isolated bacterium was initially misidentified as Aeromonas hydrophila using VITEK-2, while whole-genome sequencing (WGS) revealed that the isolate is A. dhakensis. WGS revealed the occurrence of three antimicrobial genes of resistance: imiH, cphA2, and blaOXA-12; besides, major virulence factors were detected. In silico, multilocus sequence typing (MLST) showed that our A. dhakensis 17FW001 belonged to a novel sequence type (ST557). A comparative genomic analysis of our isolate with nine selected Aeromonas species was done, which elucidated the pathogenicity of our A. dhakensis. In conclusion, we reported for the first time the association between A. dhakensis and HBV in Mainland China. We revealed that septicemic A. dhakensis could result in severe adverse clinical outcomes that end up with unexpected fulminant death especially when it is accompanied with HBV and sheds light on the virulence of A. dhakensis and the high rate of its misdiagnosis that requires to urgently consider screening of all cases of A. dhakensis for HBV in the future. Besides, caution should be taken while dealing with snakeheads which act as a vector for A. dhakensis.

A sensitive method to determine dopamine in the presence of uric acid based on In2O3 nanosheet arrays grown on 3D graphene.

A nonenzymatic voltammetric assay for dopamine (DA) was developed based on the combination of three-dimensional graphene (3D Gr) and indium oxide nanosheet arrays (In2O3 NSAs). 3D Gr was prepared by chemical vapor deposition (CVD), and In2O3 NSAs were grown on its surface by hydrothermal synthesis. The results show that 3D Gr maintains a good porous structure (200 µm), and the pore size of In2O3 NSAs is 0.50 µm. Differential pulse voltammetry (DPV) is mainly used to determine the electrochemical properties of In2O3 NSAs/3D Gr. It possesses a sensitivity of 2.69 µA·µM-1·cm-2 towards DA (5-60 µM) at 0.14 V, and the detection limit (LOD) is 0.10 µM (S/N = 3). The recoveries obtained for spiked samples in the real sample detection is 105 (± 8)%. Graphical abstractSchematic representation of DA sensitive detection by growing In2O3 nanosheets arrays on three-dimentional graphene modified ITO.

Crosstalk between autophagy and epithelial-mesenchymal transition and its application in cancer therapy.

Autophagy is a highly conserved catabolic process that mediates degradation of pernicious or dysfunctional cellular components, such as invasive pathogens, senescent proteins, and organelles. It can promote or suppress tumor development, so it is a "double-edged sword" in tumors that depends on the cell and tissue types and the stages of tumor. The epithelial-mesenchymal transition (EMT) is a complex biological trans-differentiation process that allows epithelial cells to transiently obtain mesenchymal features, including motility and metastatic potential. EMT is considered as an important contributor to the invasion and metastasis of cancers. Thus, clarifying the crosstalk between autophagy and EMT will provide novel targets for cancer therapy. It was reported that EMT-related signal pathways have an impact on autophagy; conversely, autophagy activation can suppress or strengthen EMT by regulating various signaling pathways. On one hand, autophagy activation provides energy and basic nutrients for EMT during metastatic spreading, which assists cells to survive in stressful environmental and intracellular conditions. On the other hand, autophagy, acting as a cancer-suppressive function, is inclined to hinder metastasis by selectively down-regulating critical transcription factors of EMT in the early phases. Therefore, the inhibition of EMT by autophagy inhibitors or activators might be a novel strategy that provides thought and enlightenment for the treatment of cancer. In this article, we discuss in detail the role of autophagy and EMT in the development of cancers, the regulatory mechanisms between autophagy and EMT, the effects of autophagy inhibition or activation on EMT, and the potential applications in anticancer therapy.

The relationship between autophagy and the immune system and its applications for tumor immunotherapy.

Autophagy is a genetically well-controlled cellular process that is tightly controlled by a set of core genes, including the family of autophagy-related genes (ATG). Autophagy is a "double-edged sword" in tumors. It can promote or suppress tumor development, which depends on the cell and tissue types and the stages of tumor. At present, tumor immunotherapy is a promising treatment strategy against tumors. Recent studies have shown that autophagy significantly controls immune responses by modulating the functions of immune cells and the production of cytokines. Conversely, some cytokines and immune cells have a great effect on the function of autophagy. Therapies aiming at autophagy to enhance the immune responses and anti-tumor effects of immunotherapy have become the prospective strategy, with enhanced antigen presentation and higher sensitivity to CTLs. However, the induction of autophagy may also benefit tumor cells escape from immune surveillance and result in intrinsic resistance against anti-tumor immunotherapy. Increasing studies have proven the optimal use of either ATG inducers or inhibitors can restrain tumor growth and progression by enhancing anti-tumor immune responses and overcoming the anti-tumor immune resistance in combination with several immunotherapeutic strategies, indicating that induction or inhibition of autophagy might show us a prospective therapeutic strategy when combined with immunotherapy. In this article, the possible mechanisms of autophagy regulating immune system, and the potential applications of autophagy in tumor immunotherapy will be discussed.