Enhanced local dendritic cell activity and tumor-specific immunoresponse in combined radiofrequency ablation and interleukin-2 for the treatment of human head and neck cancer in a murine orthotopic model.
BACKGROUND
Radiofrequency ablation (RFA) is a minimally invasive tumor destruction technique and can provide the antigen source initiating tumor immunity. However, induced immune response is weak and requires additional immunotherapy for optimized RFA treatment against cancer.


METHODS
A murine orthotopic model of head and neck squamous cell carcinoma (HNSCC) was established to investigate the efficacy and mechanism of an RFA + interleukin-2 (IL-2) combination adenoviral gene therapy among 6 groups. Tumor volume change, apoptosis, in situ macrophage recruitment, cytotoxic T lymphocyte (CTL) activity, migration of dendritic cells into the regional lymph nodes, and systemic antitumor immunity were examined.


RESULTS
RFA + IL-2 therapy induced the highest levels of macrophage recruitment and dendritic cell migration resulting in enhanced CTL activity, increased tumor apoptosis, enhanced systemic antitumor immunity, and the best inhibition of tumor growth among all groups.


CONCLUSIONS
RFA + IL-2 combination therapy generates potent tumor immunity to suppress tumor growth in HNSCC.
Saito
Koichiro
K
Department of Otorhinolaryngology - Head & Neck Surgery, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA.
Araki
Koji
K
Reddy
Nishant
N
Guang
Wei
W
O'Malley
Bert W
BW
Li
Daqing
D
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000276:immunology; D002294:Carcinoma, Squamous Cell / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D017115:Catheter Ablation / Q000379:methods*; D003131:Combined Modality Therapy; D003713:Dendritic Cells / Q000166:cytology* / Q000276:immunology; D004195:Disease Models, Animal; D005260:Female; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods; D006258:Head and Neck Neoplasms / Q000276:immunology / Q000401:mortality / Q000628:therapy*; D006801:Humans; D007107:Immune System / Q000276:immunology / Q000502:physiology; D007150:Immunohistochemistry; D007376:Interleukin-2 / Q000276:immunology / Q000494:pharmacology*; D008213:Lymphocyte Activation; D051379:Mice; D008809:Mice, Inbred C3H; D009368:Neoplasm Transplantation; D011897:Random Allocation; D012307:Risk Factors; D018709:Statistics, Nonparametric; D015996:Survival Rate
D007376:Interleukin-2