ABSTRACT
Summary T lymphocytes can specifically recognize tumor cells, but this interaction is known to be rather inefficient in vivo. Among other mechanims, the inadequacy of tumor destruction by T cells could stem from suboptimal activation by antigenic determinants expressed by melanoma cells. T-cell receptor (TCR) is in fact a very flexible structure capable of interacting with a broad spectrum of ligands (i.e. HLA/peptide complexes) through a versatile signaling complex. T lymphocytes have thus no single ligand specificity, but recognize a large array of HLA/peptide complexes, termed “Altered Peptide Ligands” (APL). These APL can mediate a number of different outcomes in interacting T cells, ranging from inducing selective immunological functions ( partial agonist) to completely turning off their functional capacity (antagonist). In addition to suboptimal ligands, TCR can also be triggered by superagonists, which are analogs that enhance T-cell stimulation by inducing immunological functions not detected with the cognate ligand. In this chapter we will discuss the rational for the usage of APL, that is, modified peptides from tumor antigens, to boost a potent anti-tumor T-cell reactivity cross-reacting with the native epitope expressed by cancer cell. Clinical results obtained with vaccination based on the usage of APL from tumor antigens will be additionally described. Finally, we will discuss the potential role of APL in inducing heterogeneous immune responses, including suppressive cytokine profiles, T-cell anergy and antigen-driven T-cell apoptosis, in anti-tumor lymphocytes.
