BACKGROUND: In this study, we evaluated the prognostic value of Immunoscore in patients with stage I−III colon cancer (CC) in the Asian population. These patients were originally included in an ...international study led by the Society for Immunotherapy of Cancer (SITC) on 2681 patients with AJCC/UICC-TNM stages I−III CC. METHODS: CD3+ and cytotoxic CD8+ T-lymphocyte densities were quantified in the tumor and invasive margin by digital pathology. The association of Immunoscore with prognosis was evaluated for time to recurrence (TTR), disease-free survival (DFS), and overall survival (OS). RESULTS: Immunoscore stratified Asian patients (n = 423) into different risk categories and was not impacted by age. Recurrence-free rates at 3 years were 78.5%, 85.2%, and 98.3% for a Low, Intermediate, and High Immunoscore, respectively (HRLow-vs-High = 7.26 (95% CI 1.75−30.19); p = 0.0064). A High Immunoscore showed a significant association with prolonged TTR, OS, and DFS (p < 0.05). In Cox multivariable analysis stratified by center, Immunoscore association with TTR was independent (HRLow-vs-Int+High = 2.22 (95% CI 1.10−4.55) p = 0.0269) of the patient’s gender, T-stage, N-stage, sidedness, and MSI status. A significant association of a High Immunoscore with prolonged TTR was also found among MSS (HRLow-vs-Int+High = 4.58 (95% CI 2.27−9.23); p ≤ 0.0001), stage II (HRLow-vs-Int+High = 2.72 (95% CI 1.35−5.51); p = 0.0052), low-risk stage-II (HRLow-vs-Int+High = 2.62 (95% CI 1.21−5.68); p = 0.0146), and high-risk stage II patients (HRLow-vs-Int+High = 3.11 (95% CI 1.39−6.91); p = 0.0055). CONCLUSION: A High Immunoscore is significantly associated with the prolonged survival of CC patients within the Asian population.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Abstract
Background
Invariant Natural Killer T (iNKT) cells perform pleiotropic functions in different tissues by secreting a vast array of pro-inflammatory and cytotoxic molecules. However, the ...presence and function of human intestinal iNKT cells capable to secrete immunomodulatory molecules such as IL-10 has never been reported so far. Here we describe for the first time the presence of IL10-producing iNKT cells (NKT10 cells) in the intestinal lamina propria of healthy individuals and of Crohn’s Disease (CD) patients.
Methods
Frequency and phenotype of NKT10 cells were analyzed ex-vivo from intestinal specimens of Crohn’s disease (n=17) and controls (n=7). Stable CD-derived intestinal NKT10 cell lines were used to perform in vitro suppression assays and cocultures with patients’-derived mucosa-associated microbiota. Experimental colitis models were performed by adoptive cell transfer of murine splenic naïve CD4+ T cells in the presence or absence of IL10-sufficient or deficient iNKT cells. In vivo induction of NKT10 cells was performed by administration of SCFA by oral gavage.
Results
Patient’s derived intestinal NKT10 cells demonstrated suppressive capabilities towards pathogenic CD4+ T cells. The presence of increased proportions of mucosal NKT10 cells associated with better clinical outcomes in CD patients. Moreover, an intestinal microbial community enriched in SCFA-producing bacteria sustained the production of IL10 by iNKT cells. Finally, IL10- deficient iNKT cells failed to control the pathogenic activity of adoptively transferred CD4+ T cells in an experimental colitis model.
Conclusion
These results describe an unprecedent IL10-mediated immunoregulatory role of intestinal iNKT cells in controlling the pathogenic functions of mucosal T-helper subsets and in maintaining the intestinal immune homeostasis.
The determination of the primary energy of extensive air showers using the fluorescence detection technique requires an estimation of the energy carried away by particles that do not deposit all ...their energy in the atmosphere. This estimation is typically made using Monte Carlo simulations and thus depends on the assumed primary particle mass and on model predictions for neutrino and muon production. In this work we present a new method to obtain the invisible energy from events detected by the Pierre Auger Observatory. The method uses measurements of the muon number at ground level, and it allows us to significantly reduce the systematic uncertainties related to the mass composition and the high energy hadronic interaction models, and consequently to improve the estimation of the energy scale of the Pierre Auger Observatory.
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CMK, CTK, FMFMET, IJS, NUK, PNG, UM
Molecular pathology is an integral part of daily diagnostic pathology and used for classification of tumors, for prediction of prognosis and response to therapy, and to support treatment decisions. ...For these reasons, analyses in molecular pathology must be highly reliable and hence external quality assessment (EQA) programs are called for. Several EQA programs exist to which laboratories can subscribe, but they vary in scope, number of subscribers, and execution. The guideline presented in this paper has been developed with the purpose to harmonize EQA in molecular pathology. It presents recommendations on how an EQA program should be organized, provides criteria for a reference laboratory, proposes requirements for EQA test samples, and defines the number of samples needed for an EQA program. Furthermore, a system for scoring of the results is proposed as well as measures to be taken for poorly performing laboratories. Proposals are made regarding the content requirements of an EQA report and how its results should be communicated. Finally, the need for an EQA database and a participant manual are elaborated. It is the intention of this guideline to improve EQA for molecular pathology in order to provide more reliable molecular analyses as well as optimal information regarding patient selection for treatment.
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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, VSZLJ, ZAGLJ
498.
Point defects in hexagonal silicon Sun, Lin; Marques, Mário R. G.; Marques, Miguel A. L. ...
Physical review materials,
06/2021, Volume:
5, Issue:
6
Journal Article
Peer reviewed
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CMK, CTK, FMFMET, IJS, NUK, PNG, UM
We have completed the total chemical synthesis of cytochrome b562 and an axial ligand analogue, SeMet7cyt b562, by thioester-mediated chemical ligation of unprotected peptide segments. A novel ...auxiliary-mediated native chemical ligation that enables peptide ligation to be applied to protein sequences lacking cysteine was used. A cleavable thiol-containing auxiliary group, 1-phenyl-2-mercaptoethyl, was added to the α-amino group of one peptide segment to facilitate amide bond-forming ligation. The amine-linked 1-phenyl-2-mercaptoethyl auxiliary was stable to anhydrous hydrogen fluoride used to cleave and deprotect peptides after solid-phase peptide synthesis. Following native chemical ligation with a thioester-containing segment, the auxiliary group was cleanly removed from the newly formed amide bond by treatment with anhydrous hydrogen fluoride, yielding a full-length unmodified polypeptide product. The resulting polypeptide was reconstituted with heme and folded to form the functional protein molecule. Synthetic wild-type cyt b562 exhibited spectroscopic and electrochemical properties identical to the recombinant protein, whereas the engineered SeMet7cyt b562 analogue protein was spectroscopically and functionally distinct, with a reduction potential shifted by ≈45 mV. The use of the 1-phenyl-2-mercaptoethyl removable auxiliary reported here will greatly expand the applicability of total protein synthesis by native chemical ligation of unprotected peptide segments.
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BFBNIB, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
•Ongoing hydrogeochemical monitoring network since 2002 in Tuscany, Italy.•Variations of deep originated geothermal fluids have been monitored.•CO2 positive anomaly occurred as precursor of the 2013 ...seismic swarm.
Since late 2002, a continuous automatic monitoring network is operating in Tuscany, Central Italy, to investigate the geochemical response of selected aquifers to local seismic activity. The monitoring is aimed at identifying possible earthquake geochemical precursors. The network is currently constituted by six stations, all equipped with sensors for the measurement of temperature, pH, redox potential, electrical conductivity, CO2 and CH4 dissolved concentration, that have been installed in the areas of highest seismic risk of the region. By combining geochemical data gathered from the automatic station of Gallicano (Garfagnana, Northern Tuscany), and obtained via chemical analyses of spring water samples collected during periodic field surveys in the area surrounding this station, the most significant aspects of the deep fluid circulation paths feeding the Gallicano thermo-mineral system have been investigated, and the geochemical baseline of the Gallicano spring defined. The CO2 continuous signal recorded by the Gallicano automatic station has been then processed over the period 2003–2013 in the search for anomalies possibly related to local seismic activity. A substantial anomaly in CO2 content has been observed at Gallicano in conjunction with the Alpi Apuane earthquake (M=5.2) of 21 June 2013.
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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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