Search results for " T cell"
showing 10 items of 1161 documents
Molecular and Translational Classifications of DAMPs in Immunogenic Cell Death
2015
The immunogenicity of malignant cells has recently been acknowledged as a critical determinant of efficacy in cancer therapy. Thus, besides developing direct immunostimulatory regimens, including dendritic cell-based vaccines, checkpoint-blocking therapies, and adoptive T-cell transfer, researchers have started to focus on the overall immunobiology of neoplastic cells. It is now clear that cancer cells can succumb to some anticancer therapies by undergoing a peculiar form of cell death that is characterized by an increased immunogenic potential, owing to the emission of the so-called "damage-associated molecular patterns" (DAMPs). The emission of DAMPs and other immunostimulatory factors by…
The molecular basis of cancer immunotherapy by cytotoxic T lymphocytes.
1998
The disappointing clinical results of cancer immunotherapy of the past few decades have not diminished the optimism about the potential of the new generation of immunotherapeutic strategies towards treatment of malignant disease. Tremendous progress has been made over recent years in unveiling the molecular basis of antigen presentation and recognition by cytotoxic T lymphocytes (CTL). The molecular concepts that have emerged from these studies have led to the design of novel anticancer vaccines and CTL-based immunotherapeutics. This review is to highlight the current molecular insights of antigen presentation and CTL recognition/activation, and their impact on the rational design of therap…
Generating p53-specific cytotoxic T lymphocytes by recombinant adenoviral vector-based vaccination in mice, but not man.
2002
Mutations and aberrant expression of the p53 tumor suppressor protein are the most frequent molecular alterations in human malignancy. Peptides derived from the wild-type (wt) p53 protein and presented by major histocompatibility complex (MHC) molecules for T lymphocyte recognition are believed to serve as universal tumor-associated antigens for cancer immunotherapy. We studied the immunogeneicity of a recombinant replication-defective adenoviral vector encoding human full-length wt p53 (rAd/hup53) in human leukocyte antigen (HLA)-A2K(b)-transgenic (Tg) mice and man. The generation of p53 epitope-specific cytotoxic T lymphocytes (CTLs) in p53-proficient and p53-deficient A2K(b)-Tg mice was …
Efficient Killing of Human Colon Cancer Stem Cells by γδ T Lymphocytes
2009
Abstract Colon cancer comprises a small population of cancer stem cells (CSC) that is responsible for tumor maintenance and resistant to cancer therapies, possibly allowing for tumor recapitulation once treatment stops. We previously demonstrated that such chemoresistance is mediated by autocrine production of IL-4 through the up-regulation of antiapoptotic proteins. Several innate and adaptive immune effector cells allow for the recognition and destruction of cancer precursors before they constitute the tumor mass. However, cellular immune-based therapies have not been experimented yet in the population of CSCs. Here, we show that the bisphosphonate zoledronate sensitizes colon CSCs to Vγ9…
Circumventing tolerance to a human MDM2-derived tumor antigen by TCR gene transfer
2001
We identified a tumor-associated cytotoxic T lymphocyte (CTL) epitope derived from the widely expressed human MDM2 oncoprotein and were able to bypass self-tolerance to this tumor antigen in HLA-A*0201 (A2.1) transgenic mice and by generating A2.1-negative, allo-A2.1-restricted human T lymphocytes. A broad range of malignant, as opposed to nontransformed cells, were killed by high-avidity transgenic mouse and allogeneic human CTLs specific for the A2.1-presented MDM2 epitope. Whereas the self-A2.1-restricted human T cell repertoire gave rise only to low-avidity CTLs unable to recognize the natural MDM2 peptide, human A2.1+ T lymphocytes were turned into efficient MDM2-specific CTLs upon exp…
An unconventional TRAIL to cancer therapy
2013
Cellular immunotherapy offers novel, safe, and effective routes to treating cancer. However, approaches utilizing cytotoxic CD8+ T cells are hampered by the need to identify suitable target antigens that are expressed by tumor cells but not healthy tissues, and that are recognized with sufficient affinity. Most importantly, the applicability of CD8+ T-cell-based therapies is governed by the MHC restriction of tumor-specific epitopes, thereby limiting the potential benefit to patients carrying the appropriate MHC haplotype. Alternative approaches to harness the immune system against tumors exploit non-MHC-restricted γδ T cells that recognize stress-induced changes in transformed cells. A new…
Immune Modulating Effects of NKT Cells in a Physiologically Low Dose Leishmania major Infection Model after αGalCer Analog PBS57 Stimulation
2014
Leishmaniasis is a parasitic infection affecting ∼12 million people worldwide, mostly in developing countries. Treatment options are limited and no effective vaccines exist to date. Natural Killer T (NKT) cells are a conserved innate-like lymphocyte population with immunomodulating effects in various settings. A number of reports state a role of NKT cells in different models of Leishmania infection. Here, we investigated the effect of NKT cells in a physiologically relevant, intradermal low dose infection model. After inoculation of 103 infectious-stage L. major, comparable numbers of skin-immigrating NKT cells in both susceptible BALB/c mice and resistant C57BL/6 mice were noted. Compared …
Cytokine expression profile in idiopathic inflammatory myopathies.
1996
Cytokines have been shown to be potent inducers of major histocompatibility complexes (MHC) class I and II as well as of cell adhesion molecules in muscle tissue cultures, indicating that cytokines may play a role in mediating muscle fiber damage in inflammatory myopathies. We found in 21 cases of autoimmune myositis various amounts of inflammatory cells expressing interleukin (IL)-1 alpha and -beta, IL-2, IL-4, tumor necrosis factor (TNF) -alpha and -beta, and interferon (IFN)-gamma and its receptor. Muscle fibers displayed enhanced expression of IL-1 alpha and -beta, IL-2, and TNF-alpha. Upregulation of cytokines was strongest at sites of cellular infiltration typical for the respective m…
Dendritic Cell-Specific Deletion of β-Catenin Results in Fewer Regulatory T-Cells without Exacerbating Autoimmune Collagen-Induced Arthritis.
2015
Dendritic cells (DCs) are professional antigen presenting cells that have the dual ability to stimulate immunity and maintain tolerance. However, the signalling pathways mediating tolerogenic DC function in vivo remain largely unknown. The beta-catenin pathway has been suggested to promote a regulatory DC phenotype. The aim of this study was to unravel the role of beta-catenin signalling to control DC function in the autoimmune collagen-induced arthritis model (CIA). Deletion of beta-catenin specifically in DCs was achieved by crossing conditional knockout mice with a CD11c-Cre transgenic mouse line. Bone marrow-derived DCs (BMDCs) were generated and used to study the maturation profile of …
Poly(I:C) and CpG-ODN combined aerosolization to treat lung metastases and counter the immunosuppressive microenvironment.
2015
The immunostimulatory ability of synthetic oligonucleotides containing CpG motifs (CpG-ODN), agonists of Toll-like receptor 9 (TLR9), can be harnessed to promote antitumor immunity by their application at the tumor site to stimulate local activation of innate immunity; however, particularly in the lung, tumor-associated immunosuppression can subvert such antitumor innate immune responses. To locally maintain continuous activation of innate subpopulations while inhibiting immunosuppressive cells, we evaluated aerosol delivery CpG-ODN combined with Poly(I:C), a TLR3 agonist able to convert tumor-supporting macrophages to tumoricidal effectors, in the treatment of B16 melanoma lung metastases …