Radio frequency ablation combined with interleukin-2 induces an antitumor immune response to renal cell carcinoma in a murine model.
OBJECTIVE
Immune based therapy has gained renewed interest in the search for treatment strategies for metastasized renal cell carcinoma. We determined whether radio frequency ablation combined with interleukin-2 would induce a tumor specific immune response and serve as an in situ vaccine against renal cell carcinoma.


METHODS
Mice with orthotopic renal tumors were treated with radio frequency ablation combined with interleukin-2, radio frequency ablation only, interleukin-2 only or no treatment as the control. Immunohistochemistry was done to determine which cells were present in the tumor after treatment. In vitro tumor specific cytotoxicity assays were performed with CD8+ T and natural killer cells derived from the spleen of treated mice. To study whether treatment could prevent metastasis or affect the growth of established metastases we induced lung metastasis intravenously before or after treatment and subsequently quantified it.


RESULTS
The number of natural killer, CD4+ and CD8+ T cells was significantly increased in the tumor tissue of radio frequency ablation/interleukin-2 treated mice (p <0.0001). Natural killer and CD8+ T cells showed strong antitumor activity in vitro after combination treatment. Lung metastatic formation was significantly prevented in mice that received combination therapy (p <0.0001). Lung metastases were significantly smaller after combination treatment (vs interleukin-2 p = 0.025).


CONCLUSIONS
Radio frequency ablation of the primary tumor combined with interleukin-2 induces a systemic antitumor immune response to renal cell carcinoma, which is much stronger than that of interleukin-2 monotherapy. This effect appears to be mediated by natural killer and CD8+ T cells. It may have an important role in the development of new immunotherapy strategies for renal cell carcinoma.
Department of Urology, University Medical Center Utrecht, The Netherlands.
Stephanie G C
SG
Kroeze
Laura G M
LG
Daenen
Maarten W
MW
Nijkamp
Jeanine M L
JM
Roodhart
Gijsbert C
GC
de Gast
J L H Ruud
JL
Bosch
Judith J M
JJ
Jans
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002292:Carcinoma, Renal Cell / Q000276:immunology* / Q000556:secondary / Q000628:therapy*; D017115:Catheter Ablation; D045744:Cell Line, Tumor; D003131:Combined Modality Therapy; D003601:Cytotoxicity Tests, Immunologic; D004195:Disease Models, Animal; D018450:Disease Progression; D006801:Humans; D016233:Immunotherapy, Active / Q000379:methods*; D007376:Interleukin-2 / Q000008:administration & dosage*; D007680:Kidney Neoplasms / Q000276:immunology* / Q000628:therapy*; D007694:Killer Cells, Natural / Q000276:immunology*; D008175:Lung Neoplasms / Q000276:immunology / Q000556:secondary / Q000628:therapy; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009368:Neoplasm Transplantation; D013154:Spleen / Q000276:immunology
D000970:Antineoplastic Agents; D007376:Interleukin-2