An assessment of the immunological status of patients with renal cell carcinoma based on the relative abundance of T-helper 1- and -2 cytokine-producing CD4+ cells in peripheral blood.

OBJECTIVE: To assess the immunological status of patients with renal cell carcinoma (RCC), by analysing the proportion of cluster-of-differentiation 4-positive (CD4+) cells showing intracellular cytokine production, i.e. interferon-gamma derived from T-helper (Th) 1 and interleukin-4 derived from Th2 cells, among peripheral blood lymphocytes from these patients Patients, subjects and methods Peripheral blood samples (5 mL) were collected from 36 patients (mean age 61 years, range 44-78) with RCC before and after they underwent nephrectomy. The proportion of cytokine-producing CD4+ cells was determined by flow cytometric analysis after stimulating the cells with phorbol 12-myristate 13-acetate, ionomycin and brefeldin A, and staining the cells with fluorescein isothiocyanate-labelled anti-interferon-gamma, anti-interleukin-4 and anti-immunoglubulin-2b antibodies. The results were expressed as the percentage of cytokine-producing cells in the CD4+ population. As a control, peripheral blood obtained from 35 healthy volunteers (mean age 34 years, range 22-49) was also analysed.
RESULTS: The proportion of CD4+ cells producing interferon-gamma and interleukin-4 was significantly higher (P < 0.04 and P < 0.001, respectively) in patients with RCC than in controls. The Th1/Th2 ratio (i.e. the ratio of CD4+ cells producing each cytokine) was significantly lower in patients with RCC (P < 0.001). There was a significant correlation in the controls between interferon-gamma and interleukin-4 production (r = 0.489, P < 0.01) but not in patients with RCC. The proportion of CD4+ cells producing interleukin-4 was significantly higher and the Th1/Th2 ratio significantly lower in patients with high-stage than in those with low-stage RCC (P < 0.05). The percentage of CD4+ cells producing interleukin-4 was significantly less after nephrectomy in those with low-stage RCC (P < 0.01) and the Th1/Th2 ratio significantly greater (P < 0.05) than before nephrectomy; there was no such trend in patients with high-stage RCC. Conclusion An evaluation of the production of interferon-gamma and interleukin-4 in CD4+ peripheral blood lymphocytes is useful for assessing the immunological status of patients with RCC; there is a change in the predominant response from Th1 to Th2 with increasing stage of RCC.