Premium
Immunity to cancer: attack and escape in T lymphocyte–tumor cell interaction
Author(s) -
Rivoltini Licia,
Carrabba Matteo,
Huber Veronica,
Castelli Chiara,
Novellino Luisa,
Dalerba Piero,
Mortarini Roberta,
Arancia Giuseppe,
Anichini Andrea,
Fais Stefano,
Parmiani Giorgio
Publication year - 2002
Publication title -
immunological reviews
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.839
H-Index - 223
eISSN - 1600-065X
pISSN - 0105-2896
DOI - 10.1034/j.1600-065x.2002.18809.x
Subject(s) - antigen , melanoma , biology , immunology , cancer research , epitope , t cell , tumor antigen , cytotoxic t cell , human leukocyte antigen , immunotherapy , immune system , biochemistry , in vitro
Summary: Tumor cells may express antigens which are recognized in a form of HLA/peptide complexes by T cells. The frequency at which different antigens are seen by T cells of melanoma patients and healthy donors was evaluated by human leukocyte antigen (HLA)/peptide tetramer technology which stains T cells bearing the specific receptor for a given epitope. By this technique, it was found that the majority of metastatic melanoma patients can recognize differentiation antigens (particularly Melan‐A/MART‐1), whereas such a recognition is scanty in the early phase of the disease and in healthy subjects. Despite the presence of melanoma‐specific T cells infiltrating tumor lesions, tumor rejection rarely occurs. Among the different mechanisms of such inefficient antitumor response, this review discusses the possible anti‐T‐cell counterattack mediated by FasL‐positive tumor cells, and shows that FasL is located in the cytoplasm of melanoma cells and is transported in the tumor microenvironment through the release of melanosomes. Additionally, mechanisms of suboptimal T cell activation through tumor cell expression of peptide analogs with antagonist activity are described, together with the possibility of overcoming such anergy induction by the usage of optimized tumor epitopes. Down‐modulation of HLA expression by target tumor cells and its multiple mechanisms is also considered. Finally, we discuss the role of inducible nitric oxide synthases in determining the inhibition of apoptosis in melanoma cells, which can make such tumor cells resistant to the T‐cell attack.