LYMPHOCYTOSIS DECLINE IS NOT RESPONSIBLE FOR TUMOR PROGRESSION IN CANCER-PATIENTS CHRONICALLY TREATED WITH INTERLEUKIN-2

Aims and background: The antitumor activity of IL-2 is mediated by an increase in lymphocyte number. Moreover, our previous studies have sho wn that therapy for 1 week/ month with low-dose subcutaneous IL-2 is s ufficient to maintain high levels of lymphocytes in cancer patient who have had tumor regression or stable disease (SD) in response to IL-2 immunotherapeutic cycles. This study was performed to establish whethe r tumor progression in cancer patients chronically treated with IL-2 m ay be associated with lymphocyte number decline. Methods: The study in cluded 53 metastatic renal cell cancer patients, who were treated with 2 induction cycles of IL-2 subcutaneous immunotherapy (6 million IU/d ay for 5 days/week for 6 weeks, corresponding to one cycle). Tumor reg ression occurred in 15/53 patients, 20 patients had a SD, and the rema ining 18 cases progressed. Non progressed patients (n = 35) underwent a maintenance therapy consisting of one week of therapy every month. A fter a median follow-up of 18 months, 26/35 patients with response or SD had progressed. The immune investigation consisted of lymphocyte, T lymphocyte, NK cell number determination and sCD25 level detection, R esults: The mean number of lymphocytes; T lymphocytes and NK cells obs erved on IL-2 maintenance therapy was significantly higher than that s een before beginning the immunotherapy. Moreover, mean number of lymph ocytes and mean levels of sCD25 observed at the time of tumor progress ion were respectively lower and higher than those seen on maintenance therapy in the same patients, without, however, significant difference s. Conclusion: Despite the importance of lymphocytes in medianting the antitumor activity of IL-2, this study shows that tumor progression i n cancer patients chronically treated with low-dose IL-2 after respons e or SD during IL-2 induction cycles is not associated with a signific ant decline in lymphocyte, T lymphocyte or NK cell numbers. Further st udies, carried out to analyze the functional status of immune cells at the time of tumor progression, will be necessary to define the role o f immunity in cancer patients progressing under IL-2 chronic therapy.