title: Malignancy: Changes in Circulating Immature and Mature Dendritic Cells During IL-2 Cancer Immunotherapy and Their Relation with Lymphocyte Increase and Clinical Response.
abstract: Lymphocytosis is the main biomarker predicting the efficacy of subcutaneous IL-2 anticancer immunotherapy. In addition, it has been demonstrated the fundamental role of dendritic cells (DC) in the generation of an effective anticancer immunity. However, the relation between IL-2 and DC system needs to be further understood. This preliminary study was performed in an attempt to analyze changes in circulating DC during IL-2 cancer immunotherapy in relation to lymphocyte variations and clinical efficacy of treatment. The study included 20 metastatic renal cell cancer patients, who underwent subcutaneous low-dose IL-2 immunotherapy (6.000.000 IU/day for 6 days/week for 4 weeks). To evaluate DC, venous blood samples were collected before and after 2 weeks of IL-2 injections, corresponding to the period of maximum lymphocytosis. Immature (CD123(+) ) and mature (CD11c(+) ) DC were measured by FACS and monoclonal antibodies. IL-2 induced a significant increase in the mean number of circulating mature DC, whereas no substantial change occurred in immature DC mean number. The increase in mature DC was associated with a control of disease, whereas no rise was observed in patients who had progressed on IL-2 immunotherapy. Moreover, the increase in mature DC mean number was significantly higher in patients showing evident lymphocytosis, with lymphocyte enhancement greater than 1000 cells/mmc, than in patients with less pronounced lymphocytosis, even though no significant correlation was seen in between mature DC and lymphocyte increase. This preliminary study would suggest that IL-2 may stimulate DC system and that the clinical anticancer efficacy of IL-2 is associated with the increase in circulating mature DC, which could be considered as a new favourable biomarker during IL-2 immunotherapy.
authors.affiliation: Division of Radiation Oncology, San Gerardo Hospital, Monza (Milano) Italy.
authors.forename: PAOLO
authors.initials: P
authors.lastname: Lissoni
authors.forename: ANGELA
authors.initials: A
authors.lastname: Bonfanti
authors.forename: VERONICA
authors.initials: V
authors.lastname: Bordin
authors.forename: SANDRO
authors.initials: S
authors.lastname: Barni
authors.forename: LUIGI
authors.initials: L
authors.lastname: Vigore
authors.forename: ROBERTO
authors.initials: R
authors.lastname: Ferrante
authors.forename: FRANCO
authors.initials: F
authors.lastname: Rovelli
authors.forename: LUCA
authors.initials: L
authors.lastname: Fumagalli