17 research outputs found
Marsdenia tenacissima enhances immune response of tumor infiltrating T lymphocytes to colorectal cancer
IntroductionTumor-infiltrating T lymphocytes in the tumor microenvironment are critical factors influencing the prognosis and chemotherapy outcomes. As a Chinese herbal medicine, Marsdenia tenacissima extract (MTE) has been widely used to treat cancer in China. Its immunoregulatory effects on tumor-associated macrophages is well known, but whether it regulates tumor-infiltrating T-cell functions remains unclear.MethodWe collected 17 tumor samples from MTE-administered colorectal cancer patients, 13 of which showed upregulation of CD3+/CD8+ tumor-infiltrating T cells. Further in vitro and in vivo experiments were performed to investigate the regulatory effects of MTE on tumor-infiltrating T cells and immune escape of tumors.ResultsUnder single and co-culture conditions, MTE inhibited TGF-ÎČ1 and PD-L1 expression in the colorectal cancer (CRC) cell lines HCT116 and LoVo. In Jurkat cells, MTE inhibited FOXP3 and IL-10 expression, increased IL-2 expression, but had no effect on PD-1 expression. These findings were confirmed in vitro using subcutaneous and colitis-associated CRC mouse models. MTE also increased the density of CD3+/CD8+ tumor-infiltrating T cells and exhibited considerable tumor-suppressive effects in these two tumor mouse models.ConclusionsOur findings suggested that MTE inhibits the immune escape of cancer cells, a precipitating factor increasing the immune response of T lymphocytes
Interaction between microbiota and immunity and its implication in colorectal cancer
Colorectal cancer (CRC) is one of the leading causes of cancer-related death in the world. Besides genetic causes, colonic inflammation is one of the major risk factors for CRC development, which is synergistically regulated by multiple components, including innate and adaptive immune cells, cytokine signaling, and microbiota. The complex interaction between CRC and the gut microbiome has emerged as an important area of current CRC research. Metagenomic profiling has identified a number of prominent CRC-associated bacteria that are enriched in CRC patients, linking the microbiota composition to colitis and cancer development. Some microbiota species have been reported to promote colitis and CRC development in preclinical models, while a few others are identified as immune modulators to induce potent protective immunity against colitis and CRC. Mechanistically, microbiota regulates the activation of different immune cell populations, inflammation, and CRC via crosstalk between innate and adaptive immune signaling pathways, including nuclear factor kappa B (NF-ÎșB), type I interferon, and inflammasome. In this review, we provide an overview of the potential interactions between gut microbiota and host immunity and how their crosstalk could synergistically regulate inflammation and CRC, thus highlighting the potential roles and mechanisms of gut microbiota in the development of microbiota-based therapies to prevent or alleviate colitis and CRC
Spatial Organization and Molecular Correlation of Tumor-Infiltrating Lymphocytes Using Deep Learning on Pathology Images
Beyond sample curation and basic pathologic characterization, the digitized H&E-stained images
of TCGA samples remain underutilized. To highlight this resource, we present mappings of tumorinfiltrating lymphocytes (TILs) based on H&E images from 13 TCGA tumor types. These TIL
maps are derived through computational staining using a convolutional neural network trained to
classify patches of images. Affinity propagation revealed local spatial structure in TIL patterns and
correlation with overall survival. TIL map structural patterns were grouped using standard
histopathological parameters. These patterns are enriched in particular T cell subpopulations
derived from molecular measures. TIL densities and spatial structure were differentially enriched
among tumor types, immune subtypes, and tumor molecular subtypes, implying that spatial
infiltrate state could reflect particular tumor cell aberration states. Obtaining spatial lymphocytic
patterns linked to the rich genomic characterization of TCGA samples demonstrates one use for
the TCGA image archives with insights into the tumor-immune microenvironment
Quantum Battery Based on Hybrid Field Charging
A quantum battery consisting of an ensemble two-level atom is investigated. The battery is charged simultaneously by a harmonic field and an electrostatic field. The results show that the hybrid charging is superior to the previous case of only harmonic field charging in terms of battery capacity and charging power, regardless of whether the interaction between atoms is considered or not. In addition, the repulsive interaction between atoms will increase the battery capacity and charging power, while the attractive interaction between atoms will reduce the battery capacity and discharge power
Improved Hydrogen Generation of Al-H<sub>2</sub>O Reaction by BiOX (X = Halogen) and Influence Rule
In this work, three additives BiOX (BiOI, BiOBr, and BiOF) for Al-H2O reaction have been synthesized using chemical methods. SEM analysis shows that the structure of BiOF is nanoparticles, while BiOBr and BiOI have flower-like structures composed of nanosheets. Then, Al-BiOI, Al-BiOBr, and Al-BiOF composites have been prepared using the ball milling method. The effect of halogen ions on the performance of hydrogen generation from Al hydrolysis has been explored. The results indicate that the conversion yields of Al-BiOBr, Al-BiOI, and Al-BiOF for hydrogen generation are 96.3%, 95.3%, and 8.9%, respectively. In particular, the maximum hydrogen generation rate (MHGR) of Al-BiOI is as high as 3451.8 mL gâ1 minâ1, eight times higher than that of Al-BiOBr. Furthermore, the influence rule of BiOX (X = F, Cl, Br, and I) on Al-H2O reaction has been studied using density functional theory. The results illustrate that HI can be more easily adsorbed on the Al surface as compared with HF, HCl, and HBr. Meanwhile, the bond length between halogen ions and the Al atom increased in the order of Fâ, Clâ, Brâ, and Iâ. Therefore, the dissociation of Iâ from the Al surface becomes easier and will expose more active sites to enhance the reaction activity of Al. In summary, the BiOI has the most favorable performance to Al-H2O reaction
Factors influencing advanced colorectal neoplasm anatomic site distribution in China: An epidemiological study based on colorectal cancer screening data
Abstract Objective Existing studies indicate that advanced colorectal neoplasms exhibit distinct clinical and biological traits based on anatomical sites. However, in China, especially for advanced colorectal neoplasms, there's limited information available on these traits. Our primary objective is to comprehensively study the characteristics of advanced colorectal neoplasm patients in different anatomical sites in China. Methods We selected information from the colorectal cancer screening database in Tianjin, China, since 2010 as the study subject. We chose valid information from 3113 patients with comprehensive data and diagnosed advanced colorectal neoplasms (ANs) from a pool of 19,308 individuals to be included in the study. We then conducted further analysis to examine the correlation between these epidemiological data and tumor location. Results Among the 3113 patients, neoplasms in the left side of the colon accounted for the largest proportion, while neoplasms in the right side of the colon had the smallest proportion, followed by rectal neoplasms. The highest proportion of advanced colorectal neoplasms was found among men. In the age group of 39â49âyears old, the proportion of left lateâstage advanced colon neoplasms was equal to that of right lateâstage advanced colon neoplasms, while lateâstage advanced rectal neoplasms increased with age. Smoking, drinking, and a history of colon cancer in firstâdegree relatives showed statistically significant associations with the location distribution of advanced colorectal neoplasms. A history of appendicitis, appendectomy, cholecystitis, or cholecystectomy did not significantly affect the location distribution of advanced colorectal neoplasms. However, among patients with such histories, there was a statistically significant relationship between advanced colon neoplasms on the right and those on the left and in the rectum. Similar results were observed for BMI. Conclusion Our research findings demonstrate that advanced colorectal neoplasms display unique epidemiological characteristics depending on their anatomical locations, and these distinctions deviate from those observed in Western populations. These insights contribute to a more comprehensive understanding of the topic and offer valuable guidance for future research in China. We advocate for further investigations centered on the anatomical location of colorectal neoplasms to enhance the precision of colorectal cancer (CRC) screening and treatment
Development of a TCR-like antibody and chimeric antigen receptor against NY-ESO-1/HLA-A2 for cancer immunotherapy
Background The current therapeutic antibodies and chimeric antigen receptor (CAR) T cells are capable of recognizing surface antigens, but not of intracellular proteins, thus limiting the target coverage for drug development. To mimic the feature of T-cell receptor (TCR) that recognizes the complex of major histocompatibility class I and peptide on the cell surface derived from the processed intracellular antigen, we used NY-ESO-1, a cancer-testis antigen, to develop a TCR-like fully human IgG1 antibody and its derivative, CAR-T cells, for cancer immunotherapy.Methods Human single-chain variable antibody fragment (scFv) phage library (~10â§11) was screened against HLA-A2/NY-ESO-1 (peptide 157â165) complex to obtain target-specific antibodies. The specificity and affinity of those antibodies were characterized by flow cytometry, ELISA, biolayer interferometry, and confocal imaging. The biological functions of CAR-T cells were evaluated against target tumor cells in vitro. In vivo antitumor activity was investigated in a triple-negative breast cancer (TNBC) model and primary melanoma tumor model in immunocompromised mice.Results Monoclonal antibody 2D2 identified from phage-displayed library specifically bound to NY-ESO-1157-165 in the context of human leukocyte antigen HLA-A*02:01 but not to non-A2 or NY-ESO-1 negative cells. The second-generation CAR-T cells engineered from 2D2 specifically recognized and eliminated A2+/NY-ESO-1+tumor cells in vitro, inhibited tumor growth, and prolonged the overall survival of mice in TNBC and primary melanoma tumor model in vivo.Conclusions This study showed the specificity of the antibody identified from human scFv phage library and demonstrated the potential antitumor activity by TCR-like CAR-T cells both in vitro and in vivo, warranting further preclinical and clinical evaluation of the TCR-like antibody in patients. The generation of TCR-like antibody and its CAR-T cells provides the state-of-the-art platform and proof-of-concept validation to broaden the scope of target antigen recognition and sheds light on the development of novel therapeutics for cancer immunotherapy
Organic Crosslinked Polymer-Derived N/O-Doped Porous Carbons for High-Performance Supercapacitor
Supercapacitors, as a new type of green electrical energy storage device, are a potential solution to environmental problems created by economic development and the excessive use of fossil energy resources. In this work, nitrogen/oxygen (N/O)-doped porous carbon materials for high-performance supercapacitors are fabricated by calcining and activating an organic crosslinked polymer prepared using polyethylene glycol, hydroxypropyl methylcellulose, and 4,4-diphenylmethane diisocyanate. The porous carbon exhibits a large specific surface area (1589 m2·gâ1) and high electrochemical performance, thanks to the network structure and rich N/O content in the organic crosslinked polymer. The optimized porous carbon material (COCLP-4.5), obtained by adjusting the raw material ratio of the organic crosslinked polymer, exhibits a high specific capacitance (522 F·gâ1 at 0.5 A·gâ1), good rate capability (319 F·gâ1 at 20 A·gâ1), and outstanding stability (83% retention after 5000 cycles) in a three-electrode system. Furthermore, an energy density of 18.04 Wh·kgâ1 is obtained at a power density of 200.0 W·kgâ1 in a two-electrode system. This study demonstrates that organic crosslinked polymer-derived porous carbon electrode materials have good energy storage potential
Productive replication of Middle East respiratory syndrome coronavirus in monocyte-derived dendritic cells modulates innate immune response
AbstractThe Middle East respiratory syndrome coronavirus (MERS-CoV) closely resembled severe acute respiratory syndrome coronavirus (SARS-CoV) in disease manifestation as rapidly progressive acute pneumonia with multi-organ dysfunction. Using monocyte-derived-dendritic cells (Mo-DCs), we discovered fundamental discrepancies in the outcome of MERSâCoVâ and SARS-CoV-infection. First, MERS-CoV productively infected Mo-DCs while SARS-CoV-infection was abortive. Second, MERS-CoV induced significantly higher levels of IFN-Îł, IP-10, IL-12, and RANTES expression than SARS-CoV. Third, MERS-CoV-infection induced higher surface expression of MHC class II (HLA-DR) and the co-stimulatory molecule CD86 than SARS-CoV-infection. Overall, our data suggests that the dendritic cell can serve as an important target of viral replication and a vehicle for dissemination. MERS-CoV-infection in DCs results in the production of a rich combination of cytokines and chemokines, and modulates innate immune response differently from that of SARS-CoV-infection. Our findings may help to explain the apparent discrepancy in the pathogenicity between MERS-CoV and SARS-CoV
Multiomics analysis reveals metabolic subtypes and identifies diacylglycerol kinase α (DGKA) as a potential therapeutic target for intrahepatic cholangiocarcinoma
Abstract Background Intrahepatic cholangiocarcinoma (iCCA) is a highly heterogeneous and lethal hepatobiliary tumor with few therapeutic strategies. The metabolic reprogramming of tumor cells plays an essential role in the development of tumors, while the metabolic molecular classification of iCCA is largely unknown. Here, we performed an integrated multiomics analysis and metabolic classification to depict differences in metabolic characteristics of iCCA patients, hoping to provide a novel perspective to understand and treat iCCA. Methods We performed integrated multiomics analysis in 116 iCCA samples, including wholeâexome sequencing, bulk RNAâsequencing and proteome analysis. Based on the nonânegative matrix factorization method and the protein abundance of metabolic genes in human genomeâscale metabolic models, the metabolic subtype of iCCA was determined. Survival and prognostic gene analyses were used to compare overall survival (OS) differences between metabolic subtypes. Cell proliferation analysis, 5âethynylâ2'âdeoxyuridine (EdU) assay, colony formation assay, RNAâsequencing and Western blotting were performed to investigate the molecular mechanisms of diacylglycerol kinase α (DGKA) in iCCA cells. Results Three metabolic subtypes (S1âS3) with subtypeâspecific biomarkers of iCCA were identified. These metabolic subtypes presented with distinct prognoses, metabolic features, immune microenvironments, and genetic alterations. The S2 subtype with the worst survival showed the activation of some special metabolic processes, immuneâsuppressed microenvironment and Kirsten rat sarcoma viral oncogene homolog (KRAS)/ATârich interactive domain 1A (ARID1A) mutations. Among the S2 subtypeâspecific upregulated proteins, DGKA was further identified as a potential drug target for iCCA, which promoted cell proliferation by enhancing phosphatidic acid (PA) metabolism and activating mitogenâactivated protein kinase (MAPK) signaling. Conclusion Via multiomics analyses, we identified three metabolic subtypes of iCCA, revealing that the S2 subtype exhibited the poorest survival outcomes. We further identified DGKA as a potential target for the S2 subtype