Search results for "CTL"
showing 10 items of 521 documents
On Whitham and Related Equations
2017
The aim of this paper is to study, via theoretical analysis and numerical simulations, the dynamics of Whitham and related equations. In particular, we establish rigorous bounds between solutions of the Whitham and Korteweg–de Vries equations and provide some insights into the dynamics of the Whitham equation in different regimes, some of them being outside the range of validity of the Whitham equation as a water waves model.
Modelling load-transmission mechanisms in axially loaded RC columns retrofitted with steel jackets
2018
The use of steel jacketing technique is a common practice for retrofitting existing reinforced concrete (RC) columns, as it allows increasing load-carrying capacity and ductility of the member. When the external jacket has no-end connections – i.e. the jacket is indirectly loaded- the load sustained by the column is transferred from the inner RC core to the external jacket through shear stresses along the contact surface. The assessment of this mechanism is quite complex, due to the marked non-linear behaviour of constituent materials and to the calibration of a proper shear stress-relative slip constitutive law of the concrete-to-steel interface. In this paper, a step-by-step analytical ap…
Polymorphisms in genes involved in T-cell co-stimulation are associated with blood pressure in women.
2019
In recent years, conclusive data have emerged on a relationship between immune system, especially the T-cell, and blood pressure (BP). The objective of the present study was to determine the association between BP and four polymorphisms in CD80, CD86, CD28 and CTLA4 genes that code for key proteins in the T-cell co-stimulation process, in a female cohort. To that end, an association study in a cohort of 934 women over 40 years old from two hospitals was done. Raw data showed a significant association between the SNP rs1129055 of CD86 gene and BP. Analyzing this association against inheritance patterns, higher SBP (p 0.000) and DBP (p = 0.005) values were observed in AA than in GG/GA genoty…
Short Peptide Vaccine Induces CD4+ T Helper Cells in Patients with Different Solid Cancers.
2015
Abstract Previous cancer vaccination trials often aimed to activate CD8+ cytotoxic T-cell (CTL) responses with short (8–10mer) peptides and targeted CD4+ helper T cells (TH) with HLA class II–binding longer peptides (12–16 mer) that were derived from tumor antigens. Accordingly, a study of immunomonitoring focused on the detection of CTL responses to the short, and TH responses to the long, peptides. The possible induction of concurrent TH responses to short peptides was widely neglected. In a recent phase I vaccination trial, 53 patients with different solid cancers were vaccinated with EMD640744, a cocktail of five survivin-derived short (9- or 10-mer) peptides in Montanide ISA 51VG. We m…
HLA-DPB1 mismatch alleles represent powerful leukemia rejection antigens in CD4 T-cell immunotherapy after allogeneic stem-cell transplantation.
2016
Refractory or relapsed acute myeloid leukemia (AML) represents a frequent complication after allogeneic hematopoietic stem-cell transplantation (HSCT). We show herein that primary in vitro stimulation of CD45RA-selected CD4 T cells of stem-cell donors with 10/10 HLA-matched AML blasts results in expansion of cytolytic T-lymphocytes (CTL) that almost all recognize HLA-DPB1 mismatch alleles, which clinically occur in up to 80% of donor-patient pairs. Primary AML blasts were found to strongly express HLA-DPB1, whereas fibroblasts and keratinocytes used as surrogate target cells for graft-versus-host disease did express HLA-DPB1 only upon IFN-γ pre-treatment. Since patients' AML blasts are rare…
Patient-individualized CD8+cytolytic T-cell therapy effectively combats minimal residual leukemia in immunodeficient mice
2015
Adoptive transfer of donor-derived cytolytic T-lymphocytes (CTL) has evolved as a promising strategy to improve graft-versus-leukemia (GvL) effects in allogeneic hematopoietic stem-cell transplantation. However, durable clinical responses are often hampered by limited capability of transferred T cells to establish effective and sustained antitumor immunity in vivo. We therefore analyzed GvL responses of acute myeloid leukemia (AML)-reactive CD8(+) CTL with central and effector memory phenotype in a new allogeneic donor-patient specific humanized mouse model. CTL lines and clones obtained upon stimulation of naive CD45RA(+) donor CD8(+) T cells with either single HLA antigen-mismatched or HL…
Using the r package spatstat to assess inhibitory effects of microregional hypoxia on the infiltration of cancers of the head and neck region by cyto…
2021
Simple Summary Progress in the field of in situ proteomics allows for the simultaneous detection of multiple biomarkers within one cancer tissue specimen. As a result, biological hypotheses previously only assessable ex vivo can now be studied in human cancer tissue. However, methods for objective analysis have so far been lacking behind. In this study, we established a free, objective, and entirely open-source-based method for the analysis of multiplexed immunofluorescence specimens. This will gain further importance with the availability of more advanced multiplexing methods in the future. Abstract (1) Background: The immune system has physiological antitumor activity, which is partially …
Rational Combination of Parvovirus H1 With CTLA-4 and PD-1 Checkpoint Inhibitors Dampens the Tumor Induced Immune Silencing
2019
The recent therapeutic success of immune checkpoint inhibitors in the treatment of advanced melanoma highlights the potential of cancer immunotherapy. Oncolytic virus-based therapies may further improve the outcome of these cancer patients. A human ex vivo melanoma model was used to investigate the oncolytic parvovirus H-1 (H-1PV) in combination with ipilimumab and/or nivolumab. The effect of this combination on activation of human T lymphocytes was demonstrated. Expression of CTLA-4, PD-1, and PD-L1 immune checkpoint proteins was upregulated in H-1PV-infected melanoma cells. Nevertheless, maturation of antigen presenting cells such as dendritic cells was triggered by H-1PV infected melanom…
Primary and metastatic brain cancer genomics and emerging biomarkers for immunomodulatory cancer treatment
2018
Abstract: Recent studies with immunomodulatory agents targeting both cytotoxic T-lymphocyte protein 4 (CTLA4) and programmed cell death 1 (PD1)/programmed cell death ligand 1 (PDL1) have shown to be very effective in several cancers revealing an unexpected great activity in patients with both primary and metastatic brain tumors. Combining anti-CTLA4 and anti-PD1 agents as upfront systemic therapy has revealed to further increase the clinical benefit observed with single agent, even at cost of higher toxicity. Since the brain is an immunological specialized area it's crucial to establish the specific composition of the brain tumors' micro environment in order to predict the potential activit…
Role of Hypoxia and the Adenosine System in Immune Evasion and Prognosis of Patients with Brain Metastases of Melanoma: A Multiplex Whole Slide Immun…
2020
Simple Summary The introduction of immune-checkpoint inhibitors improved the therapeutic landscape for patients with advanced malignant melanoma. However, many patients, including patients with melanoma brain metastases, do not derive benefit from immune-checkpoint blockade. Hence, biomarkers are needed to identify potential mechanisms of resistance and optimize patient selection. This study aimed to explore the role of hypoxia-mediated immunosuppression within the tumor microenvironment of patients with metastatic melanoma using multiplex immunofluorescence. We analyzed the prognostic relevance of the hypoxia surrogate marker GLUT-1, the adenosine-synthesizing ectoenzymes CD73/CD39, and th…