Clinical StudiesGranulocyte Macrophage-Colony Stimulating Factor Plus Interleukin-2 Plus α-interferon Plus 5-Fluorouracil in the Treatment of Metastatic Renal Cell Cancer Induction of CD80/86+ T Cells Indicates Adverse OutcomeWestermann, Jörg* †; Hecker, Ann-Christine* †; Flörcken, Anne*; Dörken, Bernd* †; Pezzutto, Antonio* †Author Information *Department of Hematology and Oncology, Charité, University Medicine Berlin, Campus Virchow-Klinikum †Department of Hematology, Oncology and Tumorimmunology, Charité, University Medicine Berlin, Campus Berlin-Buch Berlin, Germany Financial Disclosure: All authors have declared there are no financial conflicts of interest in regards to this work. Reprints: Jörg Westermann, Department of Hematology and Oncology, Charité, University Medicine Berlin, Campus Virchow-Klinikum, Augustenburger Platz 1, 13353 Berlin, Germany (e-mail: [email protected]). Received for publication January 31, 2009 accepted April 4, 2009 Journal of Immunotherapy: July 2009 - Volume 32 - Issue 6 - p 667-675 doi: 10.1097/CJI.0b013e3181a950e5 Buy Metrics Abstract Even in the era of multitargeted therapies, cytokines remain at least one of different treatment options in renal cell cancer (RCC), particularly for patients belonging to the good prognostic risk category according to Memorial Sloan Kettering Cancer Center criteria. Granulocyte macrophage-colony stimulating factor plays a central role in the differentiation and activation of antigen presenting cells. This clinical phase 1/2 chemoimmunotherapy trial in metastatic RCC used sequential application of α-interferon /5-fluorouracil followed by granulocyte macrophage-colony stimulating factor/interleukin-2. The study was performed before multikinase inhibitors were available for routine use. Twenty patients with metastatic RCC were enrolled into this phase 1/2 protocol. Sequential chemoimmunotherapy was feasible and safe on an outpatient basis. The regimen had only modest antitumor activity with 4 mixed responses and 4 stable diseases being documented after 4 treatment cycles. Enhanced proliferative and stimulatory capacity of peripheral blood mononuclear cells was only observed in patients with mixed responses/stable diseases whereas patients with progressive disease did not show any change. Most interestingly, there was a significant increase of T cells expressing the costimulatory molecules CD80/86 in patients with progressive disease. This finding is reported here for the first time under chemoimmunotherapy of RCC. In conclusion, clinical response rates of this cytokine-based regimen do not justify further clinical evaluation. However, the study suggests that CD80/86+ T cells might have negative regulatory function under cytokine treatment and are possibly useful as a negative predictive marker for clinical response. © 2009 Lippincott Williams & Wilkins, Inc.