Clinical responses and lymphoid infiltrates in metastatic melanoma following treatment with intralesional GM-CSF.
Past studies in animal models with gene-transfected tumour cells have suggested that GM-CSF may have a role in immunotherapy of tumours as a result of the effects it has on antigen-presenting cells. The present (phase I) studies were carried out to examine whether intralesional injections of GM-CSF induce regression of subcutaneous metastases in patients with melanoma and influence lymphoid infiltrates in and around the metastases. Thirteen patients had 15-50 mg doses of GM-CSF injected into two subcutaneous metastases. In each case one metastasis received only five injections before excision whereas the other received weekly injections up to 6 months. Partial regression of injected and/or non-injected metastases was seen in three patients. The metastases from the responding patients that were treated with intralesional GM-CSF had marked increases and high absolute numbers of T cell infiltrates into the tumour, particularly of the CD4 T cell subset. There was an increase in IL-2R expression on the T cells and an increase in the number of Langerhans' cells infiltrating the tumours. The best predictors of clinical responses therefore appeared to be high relative increases and high absolute numbers of CD4+ T cells and Langerhans' cells within the treated tumour. These results provide support for further exploration of the role of GM-CSF in immunotherapy of human melanoma.
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Immunology and Oncology Unit, Newcastle, NSW, Australia.
Hersey
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Coates
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AS
D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal; D000918:Antibody Specificity; D015703:Antigens, CD / Q000032:analysis; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000009:adverse effects* / Q000627:therapeutic use*; D015395:Histocompatibility Antigens Class I / Q000032:analysis; D000949:Histocompatibility Antigens Class II / Q000032:analysis; D006801:Humans; D007150:Immunohistochemistry; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology* / Q000473:pathology; D008297:Male; D008545:Melanoma / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D008875:Middle Aged; D009362:Neoplasm Metastasis; D012878:Skin Neoplasms / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000473:pathology
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D016178:Granulocyte-Macrophage Colony-Stimulating Factor