T-cell recognition of melanoma antigens and its therapeutic applications.
During the last few years, tumor immunology has gained impetus due to the molecular definition of T-cell-recognized antigens and the mechanisms of such recognition, antigen processing, and presentation. To date, the majority of the identified melanoma antigens are shared among different melanomas and some are also expressed in tumors of different histology. However, unique antigens expressed solely by the melanoma autologous to the T-cell used for their characterization were also found. The identification of the immunogenic peptides, the minimal target entity required for T-cell recognition, has provided novel reagents for the development of peptide-based immunotherapy. These findings, together with the understanding of requirements for T-lymphocyte recognition and activation, allow the design of new therapeutic protocols. In addition, the large body of data now available on the fine mechanism of antigen processing and presentation have revealed not only the role of the MHC molecules but also that of other intracellular proteins, such as transporter associated with antigen processing-1 and -2 and proteosome-related molecules. These findings suggest that, in order to select patients eligible for vaccination, the expression of the MHC allele involved in T-cell recognition, the profile of tumor antigens, and the status of the antigen-processing system should be carefully evaluated in tumors cells of prospective patients. In this review, some of the basic concepts of immune recognition and the current view of melanoma tumor antigens recognized by T-lymphocytes will be discussed along with the potential application of these findings in designing new therapeutic strategies.
Castelli
C
C
Division of Experimental Oncology D, Istituto Nazionale per lo Studio e la Cura dei Tumori, Milan, Italy.
Rivoltini
L
L
Mazzocchi
A
A
Parmiani
G
G
D000595:Amino Acid Sequence; D000818:Animals; D000951:Antigens, Neoplasm / Q000235:genetics / Q000276:immunology*; D004273:DNA, Neoplasm / Q000032:analysis; D006801:Humans; D007167:Immunotherapy; D008545:Melanoma / Q000276:immunology* / Q000628:therapy*; D008969:Molecular Sequence Data; D013601:T-Lymphocytes / Q000276:immunology*
D000951:Antigens, Neoplasm; D004273:DNA, Neoplasm