Search results for "CD8"
showing 10 items of 682 documents
Exome Sequencing to Predict Neoantigens in Melanoma
2015
Abstract The ability to use circulating peripheral blood cells and matched tumor sequencing data as a basis for neoantigen prediction has exciting possibilities for application in the personalized treatment of cancer patients. We have used a high-throughput screening approach, combining whole-exome sequence data, mRNA microarrays, and publicly available epitope prediction algorithm output to identify mutated proteins processed and displayed by patient tumors and recognized by circulating immune cells. Matched autologous melanoma cell lines and peripheral blood mononuclear cells were used to create mixed lymphocyte tumor cell cultures, resulting in an expansion of tumor-reactive T cells to u…
Abstract 4054: Mast cells contribute to T cell tolerance against prostate cancer- associated antigens favoring tumor growth
2015
Abstract Treatments for hormone refractory and metastatic prostate cancer (PC) still remain palliative. Also tumor specific vaccinations when tested in the clinical setting showed results lower than expected. A major limitation to active immunotherapy relies on mechanisms of tolerance adopted by the tumor. Indeed, an immunosuppressive environment is established in PC patients, as well as in the TRAMP mouse model of PC, in which peripheral T cell tolerance to the tumor-associated antigen Tag is acquired early during neoplastic transformation, with mechanisms that still need to be fully clarified. Mast cells (MCs) have been described to mediate immunological tolerance in transplantation and i…
In the literature: August 2020.
2020
Immune checkpoint inhibitors (ICI) have become a key component of therapy for several solid tumours. In patients diagnosed with advanced clear cell renal cell carcinoma (ccRCC), immunotherapy has always been considered as a treatment option, and anti-PD-1-based therapies are approved in both the frontline and refractory settings. Response to PD-1 blockade has been associated with numerous tumour-intrinsic and microenvironment features. Genetic characterisation of ccRCC has significantly contributed to the knowledge of tumour biology and the mechanisms of disease progression, but the interplay of genomic alterations with patterns of immune infiltration in response to PD-1 blockade remains un…
7 Evolution of cross-resistance to CD8+ T cells in the course of BRAF and MEK inhibitor treatment in BRAFV600E melanoma
2018
Introduction The BRAFV600 mutation, expressed in approximately 50% of melanomas, mediates constitutive activation of the BRAF-MEK-ERK in the MAPK signalling pathway and therefore tumour proliferation. Rapid and high rate of clinical responses can be achieved by targeting this axis using BRAF V600 inhibitor (BRAFi) as single therapy or the combination of BRAFi and MEKi (BRAFi/MEKi). But still disease progresses in the majority of treated patients due to acquired resistance in tumour cells. Combining targeted therapy with immunotherapy is proposed to improve the long-term outcomes of patients. However, to which extent BRAFi may affect melanoma immunogenicity over time remains largely unknown.…
Prognostic significance of spatial and density analysis of T lymphocytes in colorectal cancer.
2022
Abstract Background Although high T cell density is a strong favourable prognostic factor in colorectal cancer, the significance of the spatial distribution of T cells is incompletely understood. We aimed to evaluate the prognostic significance of tumour cell-T cell co-localisation and T cell densities. Methods We analysed CD3 and CD8 immunohistochemistry in a study cohort of 983 colorectal cancer patients and a validation cohort (N = 246). Individual immune and tumour cells were identified to calculate T cell densities (to derive T cell density score) and G-cross function values, estimating the likelihood of tumour cells being co-located with T cells within 20 µm radius (to derive T cell p…
mTOR Inhibition Improves Antitumor Effects of Vaccination with Antigen-Encoding RNA
2013
Abstract Vaccination with in vitro transcribed RNA encoding tumor antigens is an emerging approach in cancer immunotherapy. Attempting to further improve RNA vaccine efficacy, we have explored combining RNA with immunomodulators such as rapamycin. Rapamycin, the inhibitor of mTOR, was used originally for immunosuppression. Recent reports in mouse systems, however, suggest that mTOR inhibition may enhance the formation and differentiation of the memory CD8+ T-cell pool. Because memory T-cell formation is critical to the outcome of vaccination aproaches, we studied the impact of rapamycin on the in vivo primed RNA vaccine-induced immune response using the chicken ovalbumin-expressing B16 mela…
Analysis of TCR Vbeta repertoire and cytokine gene expression in patients with idiopathic dilated cardiomyopathy
2001
Although the etiopathogenesis of idiopathic dilated cardiomyopathy (IDC) is still unclear, it is widely accepted that a complex interplay between viral infections and immune mechanisms is the basis of disease genesis. Previously, we showed that heart-infiltrating T cells of patients suffering from acute, fulminant Coxsackie virus B3+-IDC shared a preferential usage of three variable gene segments of the T cell receptor beta chain-(TCR-Vbeta) encoding families Vbeta3, 7 and 13.1. This indicated the possible presence of a superantigen-driven immune response. Here, we further investigated the IDC immunological scenario by analysing different phenotypes of heart-infiltrating cells: TCR repertoi…
NKG2D induces Mcl-1 expression and mediates survival of CD8 memory T cell precursors via phosphatidylinositol 3-kinase.
2013
Abstract Memory formation of activated CD8 T cells is the result of a specific combination of signals that promote long-term survival and inhibit differentiation into effector cells. Much is known about initial cues that drive memory formation, but it is poorly understood which signals are essential during the intermediate stages before terminal differentiation. NKG2D is an activating coreceptor on Ag-experienced CD8 T cells that promotes effector cell functions. Its role in memory formation is currently unknown. In this study, we show that NKG2D controls formation of CD8 memory T cells by promoting survival of precursor cells. We demonstrate that NKG2D enhances IL-15–mediated PI3K signalin…
Cladribine exerts an immunomodulatory effect on human and murine dendritic cells
2014
Cladribine is a purine nucleoside analog developed to treat lymphoid malignancies. Reported therapeutic benefits for the autoimmune disease multiple sclerosis indicate additional immunomodulatory effects beyond the well-characterized cytotoxic activity causing lymphopenia. Here, we demonstrate that cladribine reduces the secretion of inflammatory cytokines and chemokines by murine and human dendritic cells, the most potent antigen-presenting cells. This compound also modulates the expression of the activation markers CD86 and MHC II. Furthermore, cladribine affects the T cell priming capacity of dendritic cells, resulting in reduced induction of interferon-γ- and tumor necrosis factor-α-pro…
Concentration-dependent T cell activation by different types of proteins
2009
We investigated the concentration-dependent stimulation of T cells by different human proteins. Quantitative changes in the extent of activation, as well as qualitative changes within the type of activation, were measured. At low, physiological concentrations of extracellular human proteins (0.2 µg/ml), CD4 and CD8 T lymphocytes were suppressed. In contrast, at high protein concentrations (2 mg/ml), CD4 T cells were suppressed, but we also observed a concurrent increase in the level of CD8 T cell activation. Our results are consistent with the phenomenon of cross-presentation, whereby the addition of intracellular proteins leads to the activation of both CD4 and CD8 T cells. Further additio…