Biochemotherapy of metastatic malignant melanoma. On down-regulation of CD28

Immunotherapy and combination treatments such as biochemotherapy have shown promise, with higher response rates and a subset of durable responses; however, as the majority of responses are still of short duration, they do not provide any survival benefit. There is therefore a great need to better understand the mechanisms whereby tumours escape immune surveillance. The present study examines the expression of CD28 in patients with untreated and treated melanoma metastases. Twenty-eight patients with metastatic malignant melanoma were treated by biochemotherapy (cisplatinum 30 mg/m(2) days 1-3, DTIC 250 mg/m(2) days 1-3 i.v., and IFN-alpha2b 10 million IU s.c. three days a week for 28 days treatment cycle). Tumours were resected post-biochemotherapy and analysed for the expression of CD28 in CD4(+) and CD8(+) lymphocytes in areas where histopathological regressive changes had occurred, and close to tumour cells in areas of unaffected tumour growth using a double-staining technique. A high percentage of the lymphocytes in areas with regressive changes were found to be CD4(+)CD28(-). In contrast, the vast majority of CD4(+) lymphocytes migrating close to the tumour cells were found to be CD28(+) (P