Immune Modulating Effects of Low Doses of Cyclophosphamide and Keyhole Limpet Hemocyanine on Peripheral Blood Immune Parameters in Patients with Metastatic Renal Cell Carcinoma

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Abstract
Assessing the peripheral blood immune status, we had found evidence of immunosuppression in metastatic renal cell carcinoma. Since immunosuppression might interfere with the outcome of immunotherapy, it was submitted to further investigation. Immunosuppression can be mediated by T suppressor cells, which for their part are inhibited by low-dose cyclophosphamide (Cy). We tested whether the immunomodulating effects of the biological response modifier keyhole limpet hemocyanin (KLH) on cellular and humoral immune parameters would be intensified by low-dose Cy. 10 patients were given 300 mg/m2 Cy i.v. 3 days before application of 1 mg KLH i.m. up to 8 times in 4-weekly intervals. Immune parameters were assayed twice pre-therapeutically, and prior to and 1 day and 1 week after each KLH injection. In contrast to the results obtained with KLH-mono-application, lymphocyte subsets-with the exception of T4 cell counts and the T4/T8 ratio-remained stable during the first 4 months of observation. There were increases in immunoglobulins and in the immunoactivation markers tumor necrosis factor, neopterin and beta 2-microglobulin. The tendencies found here differed from those found in a previous study on patients who were given KLH alone, and were similar to those found in patients with nonmetastatic disease who received KLH alone. However, the increases of the activation markers during KLH+Cy application were at best half as much as in patients with nonmetastatic disease. In conclusion, immunosuppression was influenced, but not counterbalanced by low-dose Cy. Most probably other mediators of immunosuppression than T suppressor cells, for example prostaglandin E2, must be considered as well.(ABSTRACT TRUNCATED AT 250 WORDS)

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