Gemcitabine plus cisplatin (GP) chemotherapy is the standard of care for nasopharyngeal carcinoma (NPC). However, the mechanisms underpinning its clinical activity are unclear. Here, using ...single-cell RNA sequencing and T cell and B cell receptor sequencing of matched, treatment-naive and post-GP chemotherapy NPC samples (n = 15 pairs), we show that GP chemotherapy activated an innate-like B cell (ILB)-dominant antitumor immune response. DNA fragments induced by chemotherapy activated the STING type-I-interferon-dependent pathway to increase major histocompatibility complex class I expression in cancer cells, and simultaneously induced ILB via Toll-like receptor 9 signaling. ILB further expanded follicular helper and helper type 1 T cells via the ICOSL-ICOS axis and subsequently enhanced cytotoxic T cells in tertiary lymphoid organ-like structures after chemotherapy that were deficient for germinal centers. ILB frequency was positively associated with overall and disease-free survival in a phase 3 trial of patients with NPC receiving GP chemotherapy ( NCT01872962 , n = 139). It also served as a predictor for favorable outcomes in patients with NPC treated with GP and immunotherapy combined treatment (n = 380). Collectively, our study provides a high-resolution map of the tumor immune microenvironment after GP chemotherapy and uncovers a role for B cell-centered antitumor immunity. We also identify and validate ILB as a potential biomarker for GP-based treatment in NPC, which could improve patient management.
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GEOZS, IJS, IMTLJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK, ZAGLJ
Early diagnosis of lung cancer is critically important to reduce disease severity and improve overall survival. Newer, minimally invasive biopsy procedures often fail to provide adequate specimens ...for accurate tumor subtyping or staging which is necessary to inform appropriate use of molecular targeted therapies and immune checkpoint inhibitors. Thus newer approaches to diagnosis and staging in early lung cancer are needed. This exploratory pilot study obtained peripheral blood samples from 139 individuals with clinically evident pulmonary nodules (benign and malignant), as well as ten healthy persons. They were divided into three cohorts: original cohort (n = 99), control cohort (n = 10), and validation cohort (n = 40). Average RNAseq sequencing of leukocytes in these samples were conducted. Subsequently, data was integrated into artificial intelligence (AI)-based computational approach with system-wide gene expression technology to develop a rapid, effective, non-invasive immune index for early diagnosis of lung cancer. An immune-related index system, IM-Index, was defined and validated for the diagnostic application. IM-Index was applied to assess the malignancies of pulmonary nodules of 109 participants (original + control cohorts) with high accuracy (AUC: 0.822 95% CI: 0.75-0.91, p < 0.001), and to differentiate between phases of cancer immunoediting concept (odds ratio: 1.17 95% CI: 1.1-1.25, p < 0.001). The predictive ability of IM-Index was validated in a validation cohort with a AUC: 0.883 (95% CI: 0.73-1.00, p < 0.001). The difference between molecular mechanisms of adenocarcinoma and squamous carcinoma histology was also determined via the IM-Index (OR: 1.2 95% CI 1.14-1.35, p = 0.019). In addition, a structural metabolic behavior pattern and signaling property in host immunity were found (bonferroni correction, p = 1.32e - 16). Taken together our findings indicate that this AI-based approach may be used for "Super Early" cancer diagnosis and amend the current immunotherpay for lung cancer.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Seeking a new method to solve the ultraviolet (UV) aging of bitumen is of great importance for road applications since the UV aging is considered to be one of the main causes leading to the ...performance deterioration of bitumen. In this paper, two UV absorbers (octabenzone and bumetrizole) were applied to modify the bitumen by melt blending. Effect of UV aging on rheology, chemistry and morphology of the UV absorber modified bitumens was investigated, by means of dynamic shear rheometer, thin-layer chromatography with flame ionization detection, Fourier transform infrared spectroscopy and atomic force microscopy, to reveal the mechanisms of action for bitumen and UV absorbers. Results show that the two UV absorbers show opposite influences on the UV aging performance of bitumen depending on the type of UV absorbers. The bumetrizole improves the UV aging resistance of bitumen remarkably since the bumetrizole can inhibit reactions of aromatization and oxidation of bitumen molecules to a certain extent during the UV aging, and thus slows down the rate at which the bitumen transforms from sol to gel. The bumetrizole modified bitumen has the potential to be used in pavement for improvement of the UV aging resistance during service life.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Tumor cells can escape immune destruction in tumor chemoresistance, but the mechanism for this phenomenon remains unclear. Y-box binding protein 1 (YB-1), which is upregulated in chemoresistant tumor ...cells, plays a role in the acquisition of multidrug resistance. Here, we demonstrate that chemotherapy induced an immunosuppressive microenvironment in the tumor and induced immune evasion through YB-1-mediated programmed death-1 ligand 1 (PD-L1) upregulation. Examination of the YB-1 protein and mRNA showed an increase in YB-1 expression in hepatocellular carcinoma (HCC). High YB-1 expression negatively correlated with the overall survival of HCC patients. YB-1 expression positively correlated with PD-L1, and YB-1 induced PD-L1 expression by binding a PD-L1 promoter motif. YB-1 expression was upregulated in chemoresistant HCC cells, and YB-1 knockdown reversed chemoresistance via T-cell activation in the tumor microenvironment due to blocked PD-L1 expression. We also found that inhibition of the tumor immunosuppressive environment and immune evasion was accompanied by proliferation of functional cytotoxic CD8
T cells and inhibition of myeloid-derived suppressor cells and regulatory T cells in the tumor environment. Our data indicate that targeting the YB-1 signaling axis, which simultaneously reverses both tumor immune evasion and multidrug resistance, may improve the antitumor response. This finding suggests a treatment modality against tumor chemoresistance.
Perivascular epithelioid cell tumor (PEComa), an uncommon mesenchymal neoplasm, arises from specialized perivascular epithelioid cells exhibiting distinct features of smooth muscle and melanocytic ...differentiation with unpredictable behavior. PEComa tends to occur more commonly in the uterus and kidneys; its occurrence in the liver is exceedingly rare. We presented a case of a 29-year-old woman with hepatic PEComa and evaluated the tumor with MRI, integrated
F-fluorodeoxyglucose (FDG), and
Ga-fibroblast activation protein inhibitor (FAPI) PET/CT scans at presentation. The patient had a history of intermittent utilization of oral contraceptive drugs for several years. An abdominal ultrasound in a physical examination from an outside institution revealed a mass in the liver. A contrast-enhanced abdominal MRI revealed restricted diffusion on diffusion-weighted imaging (DWI) and rapid contrast enhancement and washout patterns in the hepatic lesion, suggesting hepatic adenoma (HA) or hepatocellular carcinoma (HCC). Further assessment was carried out using
F-FDG and
Ga-FAPI PET/CT scans. The hepatic lesion was non-FDG avid, whereas increased tracer uptake was observed on the
Ga-FAPI PET/CT. Subsequently, laparoscopic partial resection of liver segment V was performed. Immunohistochemical analyses demonstrated positive staining for HMB45, Melan-A, and SMA while showing negative results for AFP, glypican-3, hepatocyte, and arginase-1. The results were indicative of a hepatic PEComa diagnosis based on these findings. We also review the current literature on the clinical characteristics, pathological features, and challenges in the diagnosis of hepatic PEComa.
The DArk Matter Particle Explorer (DAMPE), one of the four space-based scientific missions within the framework of the Strategic Pioneer Program on Space Science of the Chinese Academy of Sciences, ...was successfully launched on 2015 Dec. 17 from Jiuquan launch center. One of the most important scientific goals of DAMPE is to search for evidence of dark matter indirectly by measuring the spectrum of high energy cosmic-ray electrons. The neutron detector, one of the four sub-payloads of DAMPE, is designed to distinguish high energy electrons from hadron background by measuring the secondary neutrons produced in the shower. In this paper, a comprehensive introduction of the neutron detector is presented, including the design, calibration and performance. The analysis with simulated data and flight data indicates a powerful proton rejection capability of the neutron detector, which plays an essential role for TeV electron identification of DAMPE.
Classical IL-22-producing T helper cells (Th22 cells) mediate inflammatory responses independently of IFN-γ and IL-17; however, nonclassical Th22 cells have been recently identified and coexpress ...IFN-γ and/or IL-17 along with IL-22. Little is known about how classical and nonclassical Th22 subsets in human diseases are regulated. Here, we used samples of human blood, normal and peritumoral liver, and hepatocellular carcinoma (HCC) to delineate the phenotype, distribution, generation, and functional relevance of various Th22 subsets. Three nonclassical Th22 subsets constituted the majority of all Th22 cells in human liver and HCC tissues, although the classical Th22 subset was predominant in blood. Monocytes activated by TLR2 and TLR4 agonists served as the antigen-presenting cells (APCs) that most efficiently triggered the expansion of nonclassical Th22 subsets from memory T cells and classical Th22 subsets from naive T cells. Moreover, B7-H1-expressing monocytes skewed Th22 polarization away from IFN-γ and toward IL-17 through interaction with programmed death 1 (PD-1), an effect that can create favorable conditions for in vivo aggressive cancer growth and angiogenesis. Our results provide insight into the selective modulation of Th22 subsets and suggest that strategies to influence functional activities of inflammatory cells may benefit anticancer therapy.
N6-methyladenosine (m
6
A) is one of the most abundant epitranscriptomic modifications on eukaryotic mRNA. Evidence has highlighted that m
6
A is altered in response to inflammation-related factors ...and it is closely associated with various inflammation-related diseases. Multiple subpopulations of myeloid cells, such as macrophages, dendritic cells, and granulocytes, are crucial for the regulating of immune process in inflammation-related diseases. Recent studies have revealed that m
6
A plays an important regulatory role in the functional of multiple myeloid cells. In this review, we comprehensively summarize the function of m
6
A modification in myeloid cells from the perspective of myeloid cell production, activation, polarization, and migration. Furthermore, we discuss how m
6
A-mediated myeloid cell function affects the progression of inflammation-related diseases, including autoimmune diseases, chronic metabolic diseases, and malignant tumors. Finally, we discuss the challenges encountered in the study of m
6
A in myeloid cells, intended to provide a new direction for the study of the pathogenesis of inflammation-related diseases.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
With the accurate cosmic ray (CR) electron and positron spectra (denoted as Φe− and Φe+, respectively) measured by AMS-02 Collaboration, the difference between the electron and positron fluxes (i.e., ...ΔΦ=Φe−−Φe+), dominated by the propagated primary electrons, can be reliably inferred. In the standard model, the spectrum of propagated primary CR electrons at energies ≥30GeV softens with the increase of energy. The absence of any evidence for such a continuous spectral softening in ΔΦ strongly suggests a significant ‘excess’ of primary CR electrons and at energies of 100–400GeV the identified excess component has a flux comparable to that of the observed positron excess. Middle-age but ‘nearby’ supernova remnants (e.g., Monogem and Geminga) are favored sources for such an excess.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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