Increased co-expression of TIM-3 with TIGIT or 2B4 on CD8+ T cells is associated with poor prognosis in locally advanced nasopharyngeal carcinoma

The use of immune checkpoint inhibitors in malignant tumors improves patient outcomes. Because single-agent immune checkpoint blockade has a low objective response rate, it is meaningful to explore combined blockade of immune checkpoint receptors. We aimed to investigate the co-expression of TIM-3 with TIGIT or 2B4 on peripheral blood CD8+ T cells from patients with locally advanced nasopharyngeal carcinoma. The correlation between co-expression level and clinical characteristics and prognosis was studied to provide a basis for immunotherapy for nasopharyngeal carcinoma. Flow cytometry was used to detect TIM-3/TIGIT and TIM-3/2B4 co-expression on CD8+ T cells. The differences in co-expression between patients and healthy controls were analyzed. The correlation between co-expression of TIM-3/TIGIT or TIM-3/2B4 and the patient clinical characteristics and prognosis was examined. Also, the correlation between the TIM-3/TIGIT or 2B4 co-expression and other common inhibitory receptors was analyzed. We further validated our results using mRNA data from the Gene Expression Omnibus (GEO) database. TIM-3/TIGIT and TIM-3/2B4 co-expression was upregulated on peripheral blood CD8+ T cells from patients with nasopharyngeal carcinoma. They were both correlated with poor prognosis. There was a correlation between TIM-3/TIGIT co-expression and patient age and pathological stage, whereas TIM-3/2B4 co-expression correlated with age and sex. CD8+ T cells with elevated mRNA levels of TIM3/TIGIT and TIM3/2B4 also showed increased expression of multiple inhibitory receptors, indicating T cell exhaustion in locally advanced nasopharyngeal carcinoma. TIM-3/TIGIT or TIM-3/2B4 can be used as potential targets for combination immunotherapy in locally advanced nasopharyngeal carcinoma

SARS-CoV-2 mutations affect antigen processing by the proteasome to alter CD8+ T cell responses

Mutations within viral epitopes can result in escape from T cells, but the contribution of mutations in flanking regions of epitopes in SARS-CoV-2 has not been investigated. Focusing on two SARS-CoV-2 nucleoprotein CD8+ epitopes, we investigated the contribution of these flanking mutations to proteasomal processing and T cell activation. We found decreased NP9-17-B*27:05 CD8+ T cell responses to the NP-Q7K mutation, likely due to a lack of efficient epitope production by the proteasome, suggesting immune escape caused by this mutation. In contrast, NP-P6L and NP-D103 N/Y mutations flanking the NP9-17-B*27:05 and NP105-113-B*07:02 epitopes, respectively, increased CD8+ T cell responses associated with enhanced epitope production by the proteasome. Our results provide evidence that SARS-CoV-2 mutations outside the epitope could have a significant impact on proteasomal processing, either contributing to T cell escape or enhancement that may be exploited for future vaccine design

Accelerated microwave curing of fibre-reinforced thermoset polymer composites for structural applications: A review of scientific challenges

Accelerated curing of high performance fibre-reinforced polymer (FRP) composites via microwave heating or radiation, which can significantly reduce cure time and increase energy efficiency, has several major challenges (e.g. uneven depth of radiation penetration, reinforcing fibre shielding, uneven curing, introduction of hot spots etc). This article reviews the current scientific challenges with microwave curing of FRP composites considering the underlying physics of microwave radiation absorption in thermoset-matrix composites. The fundamental principles behind efficient accelerated curing of composites using microwave radiation heating are reviewed and presented, especially focusing on the relation between penetration depth, microwave frequency, dielectric properties and cure degree. Based on this review, major factors influencing microwave curing of thermoset-matrix composites are identified, and recommendations for efficient cure cycle design are provided

Broad and strong memory CD4(+)and CD8(+)T cells induced by SARS-CoV-2 in UK convalescent individuals following COVID-19

The development of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines and therapeutics will depend on understanding viral immunity. We studied T cell memory in 42 patients following recovery from COVID-19 (28 with mild disease and 14 with severe disease) and 16 unexposed donors, using interferon-γ-based assays with peptides spanning SARS-CoV-2 except ORF1. The breadth and magnitude of T cell responses were significantly higher in severe as compared with mild cases. Total and spike-specific T cell responses correlated with spike-specific antibody responses. We identified 41 peptides containing CD4+ and/or CD8+ epitopes, including six immunodominant regions. Six optimized CD8+ epitopes were defined, with peptide–MHC pentamer-positive cells displaying the central and effector memory phenotype. In mild cases, higher proportions of SARS-CoV-2-specific CD8+ T cells were observed. The identification of T cell responses associated with milder disease will support an understanding of protective immunity and highlights the potential of including non-spike proteins within future COVID-19 vaccine design

An immunodominant NP105-113-B*07:02 cytotoxic T cell response controls viral replication and is associated with less severe COVID-19 disease.

Funder: RCUK | Medical Research Council (MRC); doi: https://doi.org/10.13039/501100000265Funder: Chinese Academy of Medical Sciences (CAMS); doi: https://doi.org/10.13039/501100005150Funder: Wellcome Trust (Wellcome); doi: https://doi.org/10.13039/100004440NP105-113-B*07:02-specific CD8+ T cell responses are considered among the most dominant in SARS-CoV-2-infected individuals. We found strong association of this response with mild disease. Analysis of NP105-113-B*07:02-specific T cell clones and single-cell sequencing were performed concurrently, with functional avidity and antiviral efficacy assessed using an in vitro SARS-CoV-2 infection system, and were correlated with T cell receptor usage, transcriptome signature and disease severity (acute n = 77, convalescent n = 52). We demonstrated a beneficial association of NP105-113-B*07:02-specific T cells in COVID-19 disease progression, linked with expansion of T cell precursors, high functional avidity and antiviral effector function. Broad immune memory pools were narrowed postinfection but NP105-113-B*07:02-specific T cells were maintained 6 months after infection with preserved antiviral efficacy to the SARS-CoV-2 Victoria strain, as well as Alpha, Beta, Gamma and Delta variants. Our data show that NP105-113-B*07:02-specific T cell responses associate with mild disease and high antiviral efficacy, pointing to inclusion for future vaccine design

An Improved Measurement of the b Quark Fragmentation Function in Z{sup 0} Decays at SLD

We present preliminary results of a new measurement of the b quark fragmentation function in Z{sup 0} decays using a novel kinematic B hadron energy reconstruction technique. The measurement is performed using 150,000 hadronic Z{sup 0} events recorded in the SLD experiment at SLAC between 1996 and 1997. The small and stable SLC beam spot and the CCD-based vertex detector are used to reconstruct topological B-decay vertices with high efficiency and purity, and to provide precise measurements of the kinematic quantities used in this technique. We measure the B energy with good efficiency and resolution over the full kinematic range. We compare the scale B hadron energy distribution with several functional forms of the B hadron energy distribution and predictions of several models of b quark fragmentation. Several functions including JETSET + Peterson are excluded by the data. The average scaled energy of the weakly decaying B hadron is measured to be x{sub B} = 0.719 {+-} 0.005 (stat) {+-} 0.007 (syst) {+-} 0.001 (model) (preliminary)

Tests of QCD using Heavy Flavors in e+e-->Z0 at SLD

We present preliminary results on three SLD analyses: the gluon energy spectrum in 3-jet b{bar b}g events, the rate of g {r_arrow} b{bar b}, and the b fragmentation function in Z{sup 0} decays. The gluon energy spectrum, measured over the full kinematic range, is compared with perturbative QCD predictions. We set new 95% C.L. limits on the anomalous chromomagnetic coupling of the b quark: {minus}0.09 < {kappa} < 0.06. g{sub b{bar b}} is measured to be (3.07 {+-} 0.71 (stat) {+-} 0.66 (syst)) x 10{sup {minus}3}. The inclusive B hadron energy distribution is measured for the first time over the full kinematic range, using a novel B hadron energy reconstruction technique. Several models of b fragmentation including JETSET + Peterson are excluded by the data. The average scaled B hadron energy of the weakly decaying B hadron is measured to be x{sub B} = 0.713 {+-} 0.005 (stat) {+-} 0.007 (syst) {+-} 0.002 (model). All three measurements take advantage of the small and stable SLC interaction point as well as the excellent vertexing and tracking capabilities of the upgraded CCD-pixel vertex detector

Measurement of the B Quark Fragmentation Function in Z{sup 0} Decays

We present preliminary results of a new measurement of the inclusive b quark fragmentation function in Z{sup 0} decays using a novel kinematic B hadron energy reconstruction technique. The measurement is performed using 150,000 hadronic Z{sup 0} events recorded in the SLD experiment at SLAC between 1996 and 1997. The small and stable SLC beam spot and the CCD-based vertex detector are used to reconstruct topological B-decay vertices with high efficiency and purity, and to provide precise measurements of the kinematic quantities used in this technique. We measure the B energy with good efficiency and resolution over the full kinematic range. We compare the measured scaled B hadron energy distribution with several functional forms of the B hadron energy distribution and predictions of several models of b quark fragmentation. Several functions are excluded by the data. The average scaled energy of the weakly decaying B hadron is measured to be x{sub B} = 0.714 {+-} 0.005 (stat) {+-} 0.007 (syst) {+-} 0.002 (model) (preliminary)