Prediction of Cytokine-Therapy on Basis of Class-I and Class-II MHC Antigen Induction
Cytokine therapy has proven to be effective in approximately 15% of the patients with metastatic renal cell carcinoma (RCC). In the further implementation of this still experimental therapeutic modality, two questions are considered relevant, i.e., how can the optimal cytokine treatment combination and dosage be determined, and are there markers predicting a response. Recent findings indicate that the optimal doses can vary for individual patients . Moreover, insight into the best combination of cytokines is not yet available. In the identification of patients that respond to immunotherapy, both host mediated effects as well as tumor cell characteristics should be considered. In this study special emphasis was given to the role of histocompatibility antigens as a predictor for response. These molecules play an important role in both the presentation of autologous and or heterologous antigens to the immune system and result in eventual binding and elimination. Furthermore, it has been recognized that these molecules can be induced by several cytokines. In a previous study in which we studied the cytokine sensitivity of eight human RCC xenografts in a nude mouse model we found a variable response to the treatment with interferon-alpha, — gamme and tumor necrosis factor (TNF) . In the same model we evaluated the level of expression of histocompatibility leucocyte antigens (HLA) and the modulation by cytokines. The nude mouse model does not permit conclusions regarding the functional role of these molecules in an eventual host mediated response induced by immunotherapy; however, the expression and inducibility of HLA class-I and class-II molecules can be correlated with the nonimmune mediated antitumor response.
KeywordsRenal Cell Carcinoma Metastatic Renal Cell Carcinoma Tumor Line Nude Mouse Model Cytokine Therapy
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- 2.Aulitzky W, Gastl G, Aulitzky WE, et al. (1990) Successful treatment of metastatic renal cell carcinoma with a biologically active dose of recombinant interferon-gamma. J Clin Oncol 7: 1875–1884Google Scholar
- 5.Beniers AJMC, Peelen WP, Schaafsma HE, Beck JLM, Debruyne FMJ, Schalken JA (1991) Establishment and characterization of five new renal tumor xenografts. Am J Path (in press )Google Scholar