IMMUNOLOGICAL MONITORING OF BIOTHERAPY FOR DISSEMINATED RENAL-CELL CARCINOMA

Abstract

Objective: to assess a role of immunomonitoring in patients with disseminated renal-cell carcinoma.  

Subjects and methods. One hundred and seventy-five patients treated in 1998 to 2008 were followed up. The patients received various immunochemotherapy regimens including interleukin-2 (IL-2), interferon-α (IFN-α), Xeloda, cyclophosphamide. The immune status, including lymphocytes and their subpopulations, cytokine components (IL-1, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12; IFN-α, IFN-γ; tumor necrosis factor-α (TNF-α)), immunoglobulins (IgA, IgG, IgM), complement components (C1q, C3, C3a, C4, C5a), was evaluated before treatment and at therapy-free intervals.

 Results.  The time course of changes in cytokines (IL-6, IL-8, IL-10; TNF-α and IFN-γ) and some lymphocyte subpopulations (CD4+CD8+, CD3-CD16+CD56+, CD3+CD16+CD56+, CD4+CD25+Foxp3) greatly differs in patients who belong to different prognostic groups according to the Memorial Sloan-Kettering Cancer Center (MSKCC) inclusion criteria. Multivariate analysis has shown that the levels of IL-6 (spontaneous and induced production), IL-8 (spontaneous and induced production), TNF-α (spontaneous production), IFN-γ (induced production), NK T cells (CD3+CD16+CD56+), regulatory T cells (CD4+CD25+Foxp3) affect survival. Integration of the above indices into the MSKCC scale revealed that the groups were prognostically heterogeneous. The median survival in patients with good prognosis was 36.2 months (50.3, 38.3, and 24.5 months in those with 0—1, 2—3, and more than 3 immunological factors, respectively) and in those with relatively good and poor prognosis it was 15.3 (29.1, 15.3, and 18.1 months) and 8.5 (12.1, 9.3, and 6.3 months) months, respectively.

Conclusion. The cytokine status reflects the aggressiveness of a tumor process. The cytokine level changes may be used to predict the out- come of the disease.