Massive expansion of regulatory T-cells following interleukin 2 treatment during a phase I-II dendritic cell-based immunotherapy of metastatic renal cancer

作者：Lemoine Francois M^*; Cherai Mustapha; Giverne Camille; Dimitri Dalia; Rosenzwajg Michelle; Trebeden Negre Helene; Chaput Nathalie; Barrou Benoit; Thioun Nicolas; Gattegnio Bernard; Selles Frederic; Six Alain; Azar Nabih; Lotz Jean Pierre; Buzyn Agnes; Sibony Mathilde; Delcourt Annick; Boyer Olivier; Herson Serge; Klatzmann David; Lacave Roger

来源：International Journal of Oncology, 2009, 35(3): 569-581.

DOI：10.3892/ijo_00000368

• immunotherapy
• dendritic cells
• renal cell carcinoma
• CD34(+) cells
• interleukin 2
• regulatory T-cells

Cytotoxic chemotherapy is ineffective in metastatic renal cancer. However, systemic administration of interleukin 2 (IL-2) or infusion of dendritic cells (DCs) loaded with tumor extracts can lead to some response rates with concomitant survival improvements. We report the results of a phase I-II pilot study combining DCs and IL-2 where six patients were included. DCs were derived from bone marrow CD34(+) cells and loaded with autologous tumor extracts. CD34-DC vaccines were infused subcutaneously at day 45, 52, 59, 90 and 120 following surgery in combination with IL-2, that was subsequently administrated after the 3rd and 4th DC vaccinations. Preparation of tumor extracts and CD34-DCs were satisfactory in all patients but one. Due to rapid tumor progression, one patient was excluded before vaccination. In the 4 remaining, patients, two received 3 vaccinations, while the 2 others received 5 vaccinations and the full IL-2 treatment. No adverse effect due to the vaccinations was observed. A specific immune response against autologous tumor cells was observed in the 2 patients who completed the treatment. Interestingly, these 2 patients had a more prolonged survival than the patients receiving 3 vaccinations. Importantly, a transient and massive increase of circulating natural regulatory T-cells (nTregs) was evidenced in 3 patients following IL-2 administration. Overall, the use of CD34-DC vaccines is feasible, safe and non-toxic. A specific antitumor immune response can be detected. However, our data highlights that IL-2 is a potent inducer of nTregs in vivo and as such may have a negative impact on cancer immunotherapy.

• 出版日期2009-9