Head and neck squamous cell carcinomas (HNSCC) represent a group of metastasizing tumors with a high mortality rate in man and animals. Since the biomolecule ozone was found to inhibit growth of various carcinoma cells in vitro we here applied the highly aggressive and lethal VX2 carcinoma HNSCC tumor model of the New Zealand White rabbit to test whether ozone exerts antitumorous effects in vivo. Therapeutic insufflation of medical ozone/oxygen (O 3 /O 2 ) gas mixture into the peritoneum (O 3 /O 2 -pneumoperitoneum) at an advanced stage of tumor disease led to a survival rate of 7/14 rabbits. Six of the seven surviving rabbits presented full tumor regression and the absence of local or distant lung metastases. Key words: HNSCC; immunosurveillance; metastasis; O 3 /O 2 -pneumoperitoneum; VX2 carcinoma Squamous cell carcinomas of the head and neck region (HNSCC) frequently metastasize and show a high mortality rate in man and animals. Being an accepted animal model for studying the progression and metastatic spread of HNSCC, the highly aggressive and lethal VX2 auricular carcinoma model of the New Zealand White (NZW) rabbit 1,2 was applied in our study. This tumor model was proven to be highly suitable to investigate new therapeutic approaches, since both the HNSCC and the VX2 carcinoma are similar in growth leading to early regional lymph node and subsequent distant metastatic spread. [3][4][5] As is true for many cancers HNSCC tumor cells somehow evade the body's immune system. This immune escape can partly be explained by the frequently observed downregulation or loss of MHC Class I determinants 6,7 and an increase in CD41CD251 regulatory T cells (T reg ) that are found responsible for depressed antitumor immunity. 8-10 Therefore, being able to activate the immunosurveillance toward HNSCC tumor cells should help in recognition and eradication of this tumor entity. Enhancing the immunosurveillance capacity is an emerging concept in recent cancer immunotherapies, 11-13 particularly those focusing on immunomodulators or upregulators of the immune response. 14 To augment the host's immune response against cancer cells, therapies with recombinant cytokines, dendritic cell immunization and tumor antigen vaccination as well as T cell-based immunotherapies are currently under investigation. [15][16][17]
