Search results for "Immunologic"
showing 10 items of 1115 documents
Atypical Human Effector/Memory CD4(+) T Cells With a Naive-Like Phenotype
2018
The induction of adaptive immunological memory, mediated by T and B cells, plays an important role in protective immunity to pathogens induced by previous infections or vaccination. Naive CD4+ T cells that have been primed by antigen develop into memory or effector cells, which may be distinguished by their capability to exert a long-term and rapid response upon re-challenge by antigen, to produce distinct cytokines and surface marker expression phenotypes such as CD45RA/RO, CD27, CD62L, and CCR7. Moreover, a distinct lineage of memory T cells populates tissues (tissue-resident memory T cells or TRM cells) which orchestratea the response to pathogens re encountered at tissue sites. Recent e…
PLGA Nanoparticles Co-encapsulating NY-ESO-1 Peptides and IMM60 Induce Robust CD8 and CD4 T Cell and B Cell Responses
2021
Contains fulltext : 232076.pdf (Publisher’s version ) (Open Access) Tumor-specific neoantigens can be highly immunogenic, but their identification for each patient and the production of personalized cancer vaccines can be time-consuming and prohibitively expensive. In contrast, tumor-associated antigens are widely expressed and suitable as an off the shelf immunotherapy. Here, we developed a PLGA-based nanoparticle vaccine that contains both the immunogenic cancer germline antigen NY-ESO-1 and an α-GalCer analog IMM60, as a novel iNKT cell agonist and dendritic cell transactivator. Three peptide sequences (85-111, 117-143, and 157-165) derived from immunodominant regions of NY-ESO-1 were se…
Optimized Protocol for the Detection of Multifunctional Epitope-Specific CD4+ T Cells Combining MHC-II Tetramer and Intracellular Cytokine Staining T…
2019
Analysis of multifunctional CD4+ T cells is fundamental for characterizing the immune responses to vaccination or infection. Major histocompatibility complex (MHC)/peptide tetramers represent a powerful technology for the detection of antigen-specific T cells by specific binding to their T-cell receptor, and their combination with functional assays is fundamental for characterizing the antigen-specific immune response. Here we optimized a protocol for the detection of multiple intracellular cytokines within epitope-specific CD4+ T cells identified by the MHC class II tetramer technology. The optimal procedure for assessing the functional activity of tetramer-binding CD4+ T cells was based o…
Monitoring of anti-vaccine CD4 T cell frequencies in melanoma patients vaccinated with a MAGE-3 protein.
2005
Abstract Quantitative evaluation of T cell responses of patients receiving antitumoral vaccination with a protein is difficult because of the large number of possible HLA-peptide combinations that could be targeted by the response. To evaluate the responses of patients vaccinated with protein MAGE-3, we have developed an approach that involves overnight stimulation of blood T cells with autologous dendritic cells loaded with the protein, sorting by flow cytometry of the T cells that produce IFN-γ, cloning of these cells, and evaluation of the number of T cell clones that secrete IFN-γ upon stimulation with the Ag. An important criterion is that T cell clones must recognize not only stimulat…
Allorestricted T lymphocytes with a high avidity T-cell receptor towards NY-ESO-1 have potent anti-tumor activity.
2009
The cancer-testis antigen NY-ESO-1 has been targeted as a tumor-associated antigen by immunotherapeutical strategies, such as cancer vaccines. The prerequisite for a T-cell-based therapy is the induction of T cells capable of recognizing the NY-ESO-1-expressing tumor cells. In this study, we generated human T lymphocytes directed against the immunodominant NY-ESO-1(157-165) epitope known to be naturally presented with HLA-A*0201. We succeeded to isolate autorestricted and allorestricted T lymphocytes with low, intermediate or high avidity TCRs against the NY-ESO-1 peptide. The avidity of the established CTL populations correlated with their capacity of lysing HLA-A2-positive, NY-ESO-1-expre…
Radiotherapy and Immunogenic Cell Death
2014
Advances in understanding the mechanisms that underlie the interplay between radiation-invoked immune responses and tumor regression are underway. Emerging applications of local radiotherapy as an immunologic adjuvant have provided radiation oncologists with a method for converting malignant cells into endogenous anticancer vaccines. The dispersion of radiotherapy-induced immune-stimulating tumor antigens released from dying tumor cells into the surrounding milieu (known as immunogenic cell death, Fig. 1), is one such exploitable process that contributes to the propagation of antitumor immunity. Downstream components of the immune system may suppress, promote, or ambiguously affect antitumo…
Analysis of antigens recognized on human melanoma cells by A2-restricted cytolytic t lymphocytes (CTL)
1993
We have pursued our analysis of potential tumor-rejection antigens recognized on human melanoma by autologous cytolytic T lymphocytes (CTL). We reported previously that 3 distinct antigens (A,B,C) were recognized on melanoma cell line SK29-MEL in association with HLA-A2. Selection for melanoma-cell variants resistant to anti-A CTL revealed that antigen A consists of at least 2 determinants (Aa, Ab) which can be lost separately. Genetic linkage between Aa and Ab was suggested by concomitant loss of Aa and Ab in an immunoselected tumor-cell variant. This variant was also resistant to an autologous CTL clone restricted by HLA-B45, indicating that this CTL may also recognize a determinant of an…
Efficacy and safety of first-line checkpoint inhibitors-based treatments for non-oncogene-addicted non-small-cell lung cancer: a systematic review an…
2021
Background: Frontline immune checkpoint inhibitors (ICI)-based regimens in non-oncogene-addicted non-small-cell lung cancer (NSCLC) have been deeply investigated. To rank the available therapeutic options, we carried out a systematic review and Bayesian meta-analysis. Methods: A comprehensive search for randomized controlled trials (RCTs) of ICI regimens, and a pairwise and a network meta-analysis (NMA) with an all-comers and a stratified strategy were conducted. Endpoints were overall survival (OS), progression-free survival (PFS), objective response rate (ORR) and treatment-related adverse events (TRAEs). Results: Nineteen RCTs involving 17 treatment regimens were included. For the all-co…
Acute myeloid leukemia (AML)-reactive cytotoxic T lymphocyte clones rapidly expanded from CD8(+) CD62L((high)+) T cells of healthy donors prevent AML…
2008
Objective Current in vitro techniques for isolating leukemia-reactive cytotoxic T lymphocytes (CTLs) from healthy donors are of relatively low efficiency and yield responder populations with unknown biological significance. This study aimed at the development of a more reliable approach, allowing generation and expansion of acute myeloid leukemia (AML)-reactive CTLs using primary in vitro stimulation. Materials and Methods We established allogeneic mini-mixed lymphocyte-leukemia cultures (mini-MLLCs) by stimulating donor CD8 + T cells with human leukocyte antigen (HLA) class I–matched AML blasts in microtiter plates. Before culture, CD8 + T cells were separated into CD62L (high)+ and CD62L …
Influence of interferon-alpha on cytokine expression by the bone marrow microenvironment--impact on treatment of myeloproliferative disorders.
1996
Myeloproliferative disorders (MPD) are characterized by several common clinical and biological features, although at the molecular level, each disease entity exhibits distinct abnormalities. IFN-alpha exerts beneficial therapeutic effects in chronic myelogenous leukemia, polycythemia vera and essential thrombocythemia, resulting in control of hematopoietic hyperplasia and, in a minority of patients, in induction of cytogenetic remission. The mechanism of action of IFN-alpha in MPD is poorly defined. Recently published in vitro findings suggest that IFN-alpha interacts with the regulation of hematopoiesis by multiple ways. Its antiproliferative activity is well known for more than a decade, …