Cellular immune response against autologous human malignant melanoma: are in vitro studies providing a framework for a more effective immunotherapy?
Data concerning the in vitro lymphocyte response against autologous tumors are reviewed, with a particular emphasis on melanoma. Evidence for such an immune response to tumors has been accumulating over the last 10 years through the work of several groups of investigators. Proliferative and/or cytotoxic responses are detectable in approximately 70% of patients with primary tumors, whereas the in vitro reaction with metastatic lesions is much less frequent. This response is mainly mediated by T lymphocytes obtained from peripheral blood, tumor lesions, and lymph nodes, but patients' suppressor cells and factors have been reported to inhibit such response. Clonal analysis revealed a low but consistent frequency of antimelanoma-specific T-cytotoxic and/or proliferating cells even in metastatic melanoma patients; such effectors are major histocompatibility complex restricted and use the T-cell receptor for tumor recognition of unique and, possibly, cross-reacting melanoma-restricted antigens. The chemical and genetic nature of such molecules remains to be defined. After the limited but biologically fundamental clinical responses achieved by adoptive immunotherapy with interleukin-2 and lymphokine-activated killers, T cells appear to lend themselves as crucial new effectors in adoptive immunotherapy of human cancer and, in particular, of melanoma.
Division of Experimental Oncology D, Istituto Nazionale Tumori, Milan, Italy.
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Parmiani
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Anichini
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Fossati
D000951:Antigens, Neoplasm / Q000276:immunology*; D006649:Histocompatibility Antigens / Q000276:immunology*; D006801:Humans; D007111:Immunity, Cellular; D007167:Immunotherapy / Q000379:methods*; D066298:In Vitro Techniques; D015979:Killer Cells, Lymphokine-Activated / Q000276:immunology; D008214:Lymphocytes / Q000276:immunology*; D008285:Major Histocompatibility Complex / Q000276:immunology; D008545:Melanoma / Q000276:immunology* / Q000628:therapy; D013601:T-Lymphocytes / Q000276:immunology
D000951:Antigens, Neoplasm; D006649:Histocompatibility Antigens; C029237:tumor-associated transplantation antigen