Interleukin-2 dose, blood monocyte and CD25+ lymphocyte counts as predictors of clinical response to interleukin-2 therapy in patients with renal cell carcinoma

Abstract

The purpose of this study was to determine immunological parameters in the peripheral blood that correlate with the clinical effect of interleukin-2 (IL-2) in patients with metastatic renal cell cancer. A group of 26 patients with metastatic renal cell cancer underwent IL-2 treatment using a 36-day schedule with continuous intravenous IL-2 infusion (3 x 10(6) units m-2 day-1) administered from days 1 to 5 and days 12 to 16. The white blood cell count and the absolute and relative number of neutrophils, lymphocytes, eosinophils and monocytes were recorded six times in peripheral blood during the treatment. Also the blood counts of T cell and NK cell subsets and cells expressing the T cell activation markers IL-2R alpha and VLA-1 were measured. The lymphokine-activated killer (LAK) cell cytotoxicity was measured either with or without additional in vitro stimulation by IL-2. Multivariate statistical analysis showed that the clinical responses were related to the administered dose of IL-2, to a low number of blood cells expressing IL-2 receptors and to a reduction in the blood monocyte count (P less than 0.05).

Modulation of immune parameters in patients with metastatic renal-cell cancer receiving combination immunotherapy (IL-2, IFNα and autologous IL-2-activated lymphocytes)

“…Alternatively, these differences between the 2 protocols may (also) have resulted from the addition of IFNa to the initial IL-2 infusions in protocol 2, as IL-2 plus IFNa have been reported to induce higher serum TNFa concentrations than IL-2 alone (Blay et al, 1992b). The effects of both treatment protocols on the evaluated immune parameters confirmed by and large other reports on high-dose IL-2-based immunotherapy regimens in patients with advanced cancer: (i) lymphopenia during IL-2 infusion, followed by rebound lymphocytosis, involving CD56+,3-NK cells and CD56-,3+, CD8-,4+ and CD8+,4-T cells (Sonde1 et al, 1988;Favrot et al, 1990;Hermann et aL, 1991;Farace et al, 1994); (ii) eosinophilia persisting during the entire treatment period Farace et al, 1994); (iii) induction of increased serum concentrations of the secondary cytokines IFNy and TNFa (Blay et al, 1990;Economou et al, 1991); (iv) induction of high levels of and LAKDaudi activities by ex vivo IL-2-activated lymphocytes, whilst those of PBMC remained within or slightly above the normal range (Phillips et al, 1987;Boldt et al, 1988;Favrot et al, 1990;Fortis et al, 1990).…”

Monocytes, Monocytic Myeloid Derived Suppressor Cells and Lymphoma: How Tight is the Knot of the Tie?

“…Furthermore the prognostic value of AMC was also examined and reported by other groups not only in lymphomas, but also in other hematological disorders such as idiopathic myelofibrosis [11], and non-hematologic malignancies, including head and neck cancer , renal cell carcinoma, and melanoma [12,13] and Similar conclusions as for lymphomas were drawn in all these studies.…”

Intratumoral CD14+ Cells and Circulating CD14+HLA-DRlo/neg Monocytes Correlate with Decreased Survival in Patients with Clear Cell Renal Cell Carcinoma

“…These cells have been shown to adversely affect survival of RCC patients treated with a multipeptide cancer vaccine (6) and impede the differentiation into fully mature dendritic cells (31). Circulating monocytes and granulocytes have previously been independently associated as prognostic factors for poor clinical responses to IL2 immunotherapy (39,40). Therefore, the synergistic interaction between tumor and monocytes may explain the ineffectiveness of many immune therapies by shutting down both local and systemic antitumor immunity.…”