The Human T Cell Response to Melanoma Antigens

Division of Clinical Onco-Immunology, Ludwig Institute for Cancer Research, Lausanne Branch, University Hospital (CHUV), Lausanne, Switzerland.
Advances in Immunology (Impact Factor: 5.96). 02/2006; 92:187-224. DOI: 10.1016/S0065-2776(06)92005-7
Source: PubMed


The cornerstone of the concept of immunosurveillance in cancer should be the experimental demonstration of immune responses able to alter the course of in vivo spontaneous tumor progression. Elegant genetic manipulation of the mouse immune system has proved this tenet. In parallel, progress in understanding human T cell mediated immunity has allowed to document the existence in cancer patients of naturally acquired T cell responses to molecularly defined tumor antigens. Various attributes of cutaneous melanoma tumors, notably their adaptability to in vitro tissue culture conditions, have contributed to convert this tumor in the prototype for studies of human antitumor immune responses. As a consequence, the first human cytolytic T lymphocyte (CTL)-defined tumor antigen and numerous others have been identified using lymphocyte material from patients bearing this tumor, detailed analyses of specific T cell responses have been reported and a relatively large number of clinical trials of vaccination have been performed in the last 15 years. Thus, the "melanoma model" continues to provide valuable insights to guide the development of clinically effective cancer therapies based on the recruitment of the immune system. This chapter reviews recent knowledge on human CD8 and CD4 T cell responses to melanoma antigens.

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    • "The main response of the immune system to tumors is to destroy the abnormal cells using killer T cells, sometimes with the assistance of helper T cells [4] [7]. Tumor antigens are presented on MHC class I molecules in a similar way to viral antigens. "

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    • "The immune system can recognize and omit tumors which express antigens that are not observed in normal cells. So such antigens are considered as foreign by the immune system, which ultimately attacks and destroys them [23] using killer T cells, and occasionally with the support of the helper T cells [24]. These antigens function as viral forms by acting on the MHC class I molecules; killer T cells recognize tumors as nonstandard cells [25]. "
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    ABSTRACT: T-cells play an important role in the immune response and are activated in response to the presentation of antigens bound to major histocompatibility complex (MHC) molecules participating with the T-cell receptor (TCR). T-cell receptor complexes also contain four CD3 (cluster of differentiation 3) subunits. The TCR-CD3 complex is vital for T-cell development and plays an important role in intervening cell recognition events. Since microRNAs (miRNAs) are highly stable in blood serum, some of which may target CD3 molecules, they could serve as good biomarkers for early cancer detection. The aim of this study was to see whether there is a relationship between cancers and the amount of miRNAs -targeted CD3 molecules. Bioinformatics tools were used in order to predict the miRNA targets for these genes. Subsequently, these highly conserved miRNAs were evaluated to see if they are implicated in various kinds of cancers. Consequently, human disease databases were used. According to the latest research, this study attempted to investigate the possible down- or upregulation of miRNAs cancer patients. We identified miRNAs which target genes producing CD3 subunit molecules. The most conserved miRNAs were identified for the CD3G gene, while CD247 and CD3EAP genes had the least number and there were no conserved miRNA associated with the CD3D gene. Some of these miRNAs were found to be responsible for different cancers, following a certain pattern. It is highly likely that miRNAs affect the CD3 molecules, impairing the immune system, recognizing and destroying cancer tumor; hence, they can be used as suitable biomarkers in distinguishing cancer in the very early stages of its development.
    PLoS ONE 11/2013; 8(11):e78790. DOI:10.1371/journal.pone.0078790 · 3.23 Impact Factor
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    • "The majority of human tumor-associated antigens are non-mutated self-antigens shared between individuals (Rosenberg, 2001). Many antigens recognized by autologous T lymphocytes have been identified on human melanoma (Romero et al., 2006). The first step in TCR-based therapy is the choice of appropriate melanoma tumor-antigens to target the T cells. "
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    ABSTRACT: Adoptive immunotherapy with tumor infiltrating lymphocytes (TILs) is a potent ther-apy for metastatic melanoma. In this process, naturally occurring tumor reactive TILs that bear T-cell receptors (TCR) targeted against tumor cells are generated ex vivo and administrated into the patients. The generation of tumor-reactive T cells is not always possible in all of the patients. To overcome this limitation, we can now insert highly avid TCRs into T cells that can recognize tumor antigens. Genetic engineering of TCR genes into normal T cells is a powerful new strategy to generate large numbers of defined antigen-specific cells for therapeutic application. This approach has evolved beyond experimental stage into a clinical reality. The feasibility of TCR-engineered T cells has been shown to be an effective clinical strategy resulting in the regression of established tumors in recent clinical trials. In this review, we discuss the progress and prospects of TCR-engineered T cells as a therapeutic strategy for treating patients with melanoma and other cancers.
    Gene Therapy and Regulation 10/2010; 1(5):67-80. DOI:10.1142/S1568558610000161
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