Five-year survival results of subcutaneous low-dose immunotherapy with interleukin-2 alone in metastatic renal cell cancer patients.

After the discovery of its essential role in anticancer immunity, IL-2 cancer immunotherapy has shown that comparable results may be obtained with different schedules, including intravenous high-dose IL-2 as a bolus or as a 24-hour intravenous infusion or prolonged subcutaneous injection of low-dose IL-2 with or without IFN-alpha. This study shows the long-term results obtained in 92 metastatic renal cell cancer (RCC) patients with low-dose subcutaneous IL-2, which was given at 3 million IU twice/day for 5 days/week for 6 consecutive weeks. In nonprogressing patients, a second cycle was planned after a 21-day rest period, followed by maintenance therapy consisting of 5 days of treatment every month until disease progression. Complete response (CR) was achieved in only 2/92 (2%) patients, and partial response (PR) was observed in 19 patients (21%). Therefore, the response rate (CR + PR) was 21/92 (23%), with a median duration of response of 25 months. Stable disease (SD) occurred in 37 patients (40%), whereas the other 34 (37%) had a progressive disease (PD). The response rate was significantly higher in patients with a disease-free interval of >1 year than in those with a lower interval, in patients with a high performance status (PS) than in those with a low PS, and in patients with sites of disease other than the liver. A 5-year survival was obtained in 9/92 (9%) patients, and the percent of survival was significantly higher in patients with a response or SD than in those with PD. The treatment was well tolerated in all patients. This study confirms that low-dose subcutaneous IL-2 alone in an effective and well tolerated therapy of metastatic RCC, with results comparable to those described with more aggressive and toxic IL-2 schedules.

Circulating dendritic cells in early and advanced cancer patients: diminished percent in the metastatic disease.

Despite the well demonstrated fundamental role of dendritic cells (DC) in generating antitumor immunity in experimental conditions, to date there are only few preliminary studies which investigate the percent of DC in the peripheral blood of cancer patients. Several cell surface markers have now been described which are specific to cultured DC, however their expression in vivo is still controversial. Recently, however, two DC subsets, consisting of immature and mature DC, have been shown to be present in peripheral blood, which can be recognized as CD123+ and CD11c+ cells, respectively. On this basis, we decided to investigate the presence of both mature and immature DC in the peripheral blood of early or advanced cancer patients. The study included 40 solid tumor patients, 18 of whom had a locally limited disease, while the other 22 showed distant organ metastases. CD123+ and CD11c+ cells were detected by FACS using monoclonal antibodies, and expressed as the percent of total leukocytes. The control group consisted of 50 healthy subjects. The mean percent of both CD123+ and CD11c+ cells was significantly lower in cancer patients than in controls. Moreover, the mean percent of both DC subsets was significantly lower in metastatic patients than in the non-metastatic ones. This study, demonstrating significantly lower percents of both immature and mature DC in the peripheral blood of cancer patients, particularly in those with distant organ metastases, suggests that DC deficiency may play a role in inducing cancer-related immunosuppression. Therefore, the demonstration of a diminished percent of DC in peripheral blood may represent a new interesting biological marker predicting a poor prognosis in human neoplasms, as with lymphocytopenia, the unfavourable prognostic significance of which has been well demonstrated.