Search results for "T cell"

Novel insights into cancer stem cells targeting: CAR-T therapy and epigenetic drugs as new pillars in cancer treatment

2023

Cancer stem cells (CSCs) represent the most aggressive subpopulation present in the tumor bulk retaining invasive capabilities, metastatic potential and high expression levels of drug efflux pumps responsible for therapy resistance. Cancer is still an incurable disease due to the inefficacy of standard regimens that spare this subpopulation. Selective targeting of CSCs is still an unmet need in cancer research field. Aberrant epigenetic reprogramming promotes the initiation and maintenance of CSCs, which are able to escape the immune system defense. Promising therapeutic approaches able to induce the selective inhibition of this stem-like small subset include immunotherapy alone or in combi…

Allogeneic Stem Cell Transplantation in Mantle Cell Lymphoma; Insights into Its Potential Role in the Era of New Immunotherapeutic and Targeted Thera…

2022

Simple Summary We present the long-term results of patients receiving allogeneic stem cell transplantation (allo-SCT) for relapsed/refractory mantle cell lymphoma (R/R MCL) in the last 25 years in Spain. We conclude that allo-SCT may be a curative option in R/R MCL with a low cumulative incidence (CI) of relapse, although non-relapse mortality (NRM) is still high, which is mainly secondary to acute graft-versus-host disease (aGVHD). Results are better for fit patients, using HLA-identical (related or unrelated) or haploidentical related donors and without previous ASCT. However, the arrival of new highly effective and low toxic immunotherapeutic or targeted therapies inevitably will relegat…

Cancer cell targeting by CAR-T cells: A matter of stemness

2022

Chimeric antigen receptor (CAR)-T cell therapy represents one of the most innovative immunotherapy approaches. The encouraging results achieved by CAR-T cell therapy in hematological disorders paved the way for the employment of CAR engineered T cells in different types of solid tumors. This adoptive cell therapy represents a selective and efficacious approach to eradicate tumors through the recognition of tumor-associated antigens (TAAs). Binding of engineered CAR-T cells to TAAs provokes the release of several cytokines, granzyme, and perforin that ultimately lead to cancer cells elimination and patient’s immune system boosting. Within the tumor mass a subpopulation of cancer cells, known…

Imaging of T cell-mediated inflammation in a preclinical GvHD model using radiolabeled anti-human CD3 antibody

2019

Defective expression of CD95 (FAS/APO-1) molecule suggests apoptosis impairment of T and B cells in HLA-B8, DR3-positive individuals.

1997

Activation-induced apoptosis is one of the primary control mechanisms for the negative selection of an immune response, leading to maintenance of immune homeostasis and selective T cell deletion. The interaction between the surface molecule Fas and its ligand (FasL) has been proposed as a primary mechanism initiating T cell apoptosis. The T cell receptor modulates the expression and function of these molecules. Defects in the Fas/FasL apoptosis pathway have been shown to result in autoimmune disease in humans and in murine models. Because subjects carrying the HLA-B8, DR3 haplotype show a number of immune dysfunctions, including membrano-proliferative glomerulonephritis, systemic lupus eryt…

Antigen-independent in vitro expansion of T cells does not affect the T cell receptor V beta repertoire.

1997

Analysis of the variable chains (V alpha/V beta) of the specific T cell receptor (TCR) of organ-infiltrating T cells may provide further insights into the pathogenesis of many infectious diseases, malignancies, and autoimmune disorders. To determine the TCR V beta repertoire of these small T cell populations antigen-independent in vitro expansion is necessary but may select for certain T cell subpopulations. In this study various antigen independent T cell activation protocols were used to stimulate peripheral blood mononuclear cells (PBMC) of six healthy blood donors, and TCR V beta molecules were analyzed by flow cytometry and semiquantitative reverse-transcriptase polymerase chain reacti…

Anti-GD3 antibodies are potent activators of human gamma/delta and alpha/beta positive T cells.

1995

The ganglioside GD3 has a variety of biological functions. These include stimulatory effects on proliferation, natural killer activity and cytokine production by freshly isolated peripheral T cells. In this study we have characterized anti-GD3 antibody (MoAb Z21) mediated effects on T cell clones. Our data indicate that alpha/beta TCR CD4+ and CD8+ as well as gamma/delta TCR positive T cells can be stimulated resulting in proliferation and cytokine production. This effect could be blocked by cyclosporin A and did not involve the LFA-3 or CD4 molecule. Apart from IFN-gamma and IL-2 production by T helper 1 and T helper 0 cells we have observed production of IL-4 and IL-10 by T helper 2 cells…

LFA-1 Contributes to Signal I of T-Cell Activation and to the Production of Th1 Cytokines

2010

The beta(2) integrins are important for both transendothelial migration of leukocytes and T-cell activation during antigen presentation. In T cells, triggering of leukocyte functional antigen-1 (LFA-1) is required for full activation and T-helper (Th)1/Th2 differentiation. We used CD18-deficient (CD18(-/-)) mice to examine the role of LFA-1 in the activation of T cells. Compared with wild-type controls, CD18(-/-) T cells proliferated normally when stimulated with antibodies against CD3 and CD28, but secreted significantly less IFN-gamma and IL-2 than their wild-type counterparts. However, when T cells were stimulated with dendritic cells (DCs) that provide additional LFA-1 ligation, the pro…

Specific Targeting of Cytokine-Secreting Cells: A Bispecific Diabody Recognizing Human Interleukin-6 and CD3 Induces T Cell-Mediated Killing

1998

Cytokines have been implicated in the pathophysiology of many diseases. Although there have been many attempts to neutralize the activity of cytokines in vivo and in vitro, no strategies have been developed to specifically eliminate cells that overexpress cytokines. Considering the fact that cytokines in part remain cell associated on secretion, we have constructed a bispecific diabody consisting of a nonneutralizing scFv antibody recognizing human interleukin-6 (IL-6) and an scFv corresponding to the monoclonal antibody (mAb) OKT3, which recognizes and activates the human T cell receptor. Here we show that the diabody recognized both human IL-6 and human CD3. In the presence of human T cel…

Differential effects of IL-10 on proliferation and cytokine production of human gamma/delta and alpha/beta T cells.

1994

Gamma/delta TCR bearing T lymphocytes represent a T-cell subset whose functional relevance remains unclear. Nevertheless these T cells may play a role in the early immune response against bacteria. Until now the regulatory mechanisms on this response have not been investigated. The study described here evaluated the immunoregulatory effects of Interleukin-10 on gamma/delta and alpha/beta TCR-positive T-cell clones and freshly isolated peripheral-blood mononuclear cells (PBMC). IL-10 has been shown previously to inhibit lectin and antigen-induced proliferation and cytokine production by alpha/beta T cells. The results outlined below show that rhIL-10 strongly inhibits lectin-induced producti…