Melanoma immunology: past, present and future.
OBJECTIVE
Metastatic melanoma is a disease for which no effective therapeutic options have been developed during the last 30 years with the possible exception of high dose interferon-alpha in the adjuvant setting of stage III patients. The immunotherapy approach was initiated decades ago using cell-based vaccines and adoptive immunotherapy with functionally ill-defined lymphocytes. This paper aims to evaluate the last three decades of research in melanoma immunotherapy and to provide insights in the future of this strategy.


RESULTS
Thanks to the development of knowledge in basic and applied immunology, clinical studies of immunotherapy have been followed by trials based on molecular characterization of melanoma antigens and availability of ex-vivo assays allowing the quantitative assessment of the immune response against the given vaccine and against patient tumor cells. This second generation of immunotherapy trials, along with additional preclinical studies, while not yet resulting in a convincing clinical outcome, provided a wealth of data on immunogenicity of different melanoma antigens, mechanism of antigen presentation and factors that impair immune recognition of melanoma cells.


CONCLUSIONS
We discuss how this information will be exploited for designing new and more successful clinical trials of both active and adoptive antigen-specific immunotherapy of metastatic melanoma patients.
Parmiani
Giorgio
G
Unit of Immunotherapy of Human Tumors, Istituto Nazionale Tumori Foundation, Milan, Italy. giorgio.parmiani@istitutotumori.mi.it
Castelli
Chiara
C
Santinami
Mario
M
Rivoltini
Licia
L
D015536:Down-Regulation; D006801:Humans; D007167:Immunotherapy / Q000639:trends; D008545:Melanoma / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*