Can oncogene (RAS) activation predict susceptibility of human melanoma to activated lymphocytes and, therefore, the clinical response of such neoplasms to adoptive immunotherapy?
The expression of activated ras oncogenes was found to be associated with that of tumour-specific transplantation antigens in mouse tumours, which can be cured by adoptive immunotherapy with T lymphocytes and interleukin-2 (IL-2). A similar association is here proposed to exist between RAS oncogene activation (mutation) in human melanoma and susceptibility of these tumours to the lytic action of activated lymphocytes (both lymphokine-activated killers and cytotoxic T cells) which have been used, along with IL-2, in the adoptive immunotherapy of advanced melanomas. The limited clinical response (15-25%) of melanoma patients to different immunological therapies is, therefore, considered to be due to a similar frequency of immunogenic, RAS+ melanomas. The authors thus suggest that RAS activation might be a marker of immunogenicity and that only the subset of melanoma cells expressing activated RAS will in turn possess tumour antigens which can be the target of immunotherapeutic, activated lymphocytes. It is then predicted that RAS+ melanomas will be more susceptible to adoptive immunotherapy than RAS-counterparts.
Parmiani
G
G
Division of Experimental Oncology D, Istituto Nazionale Tumori, Milan, Italy.
Anichini
A
A
Carbone
G
G
Sensi
M
M
D000818:Animals; D011905:Genes, ras; D006801:Humans; D016219:Immunotherapy, Adoptive; D008213:Lymphocyte Activation; D008545:Melanoma / Q000235:genetics* / Q000276:immunology* / Q000628:therapy; D009154:Mutation