Purpose: How tumors evade or suppress immune surveillance is a key question in cancer research, and overcoming immune escape is a major goal for lengthening remission after cancer treatment. Here, we used the papillomavirus-associated rabbit auricular VX2 carcinoma, a model for studying human head and neck cancer, to reveal the mechanisms underlying the antitumorigenic effects of intraperitoneal oxidative stressExperimental Design: Solid auricular VX2 tumors were induced in immune-competent adult New Zealand White Rabbits. Animals were O 3 /O 2 -PP-or sham-treated, after which they underwent tumor ablation upon reaching no-go criteria. CD3 þ tumor-infiltrating lymphocytes (TIL) were evaluated by immunohistochemistry, and expression levels of 84 immune response genes were measured by quantitative real-time PCR. Adoptive transfer of peripheral blood leukocytes (PBL)-derived from animals with tumor regression-into control animals with progressing tumors was implemented to assess acquired tumor resistance functionally. Results: Auricular VX2 tumors regressing after O 3 /O 2 -PP treatment exhibited increased levels of CD3 þ TILs; they also exhibited enhanced expression of genes that encode receptors involved in pattern recognition, molecules that are required for antigen presentation and T cell activation, and inflammatory mediators. Adoptive cell transfer of PBLs from donor rabbits with regressing tumors to recipient rabbits with newly implanted VX2 carcinoma resulted in acquired tumor resistance of the host and tumor regression. Conclusion: Intraperitoneal oxidative stress effectively converts the immune response against the papillomavirus-associated rabbit VX2 carcinoma from tumor permissive to tumoricidal and leads to a sustainable, adoptively transferable oncolytic immune response. Clin Cancer Res; 20(16); 4289-301. Ó2014 AACR.

The ability of integrated (18)F-fluorodeoxyglucose positron emission tomography and computed tomography (FDG PET/CT) to distinguish between benign and malignant incidental non-secreting adrenal masses was evaluated in cancer patients. Results were compared with those of CT and shift magnetic resonance imaging (MRI). A total of 1832 cancer patients who had undergone FDG PET/CT scans were retrospectively evaluated. Visual interpretation, tumour maximum standardized uptake value (SUV(max)), liver SUV(max) and tumour/liver SUV(max) ratios were correlated with the findings of CT, shift MRI and final diagnosis (based on biopsy or clinical/radiological follow-up). A total of 109 adrenal masses were found: 49 were malignant and 60 were benign on final diagnosis. A tumour/liver SUV(max) ratio threshold of 1.0 was more accurate in differentiating the tumour type than tumour SUV(max) or visual interpretation alone. Diagnostic accuracy of CT and shift MRI (92 - 97%) was similar to that for FDG PET/CT (94 - 97%). In conclusion, FDG PET/CT accurately characterizes adrenal tumours, with excellent sensitivity and specificity. Use of 1.0 as the threshold for the tumour/liver SUV(max) ratio seems to be promising for distinguishing benign from malignant adrenal masses in cancer patients.

Preoperatively, a total of nine SLNs were located in five patients with fhSPECT. SLNs in three patients were positive for metastatic disease; in two patients the SLNs were tumor-free. No residual radioactivity was found in the neck in any of the patients after extirpation of SLNs. fhSPECT acquisitions took 2.6 ± 0.4 min. No metastatic lymph nodes were detected in any other node harvested during subsequent selective neck dissection in any patients.

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<p>Supplementary Table 1. Hemogram of rabbits, which respond to O3/O2-PP treatment by tumor clearance (n=7) and of rabbits, which showed a clear tumor progression after sham treatment (n=6). Blood parameters were measured before induction of the auricular VX2 tumor (base value) and of VX2 tumor bearing rabbits directly before and after the treatment schema. ‡ The base value includes blood parameter from animals of both treatment schema (n=13). Statistically significant changes between values before and after a treatment were marked with p<0.05. Abbreviations: WBC (White blood cells), RBC (Red blood cells), PLT (Platelets), HGB (Hemoglobin), HCT (Hematocrit), MCV (mean corpuscular volume), MCH (mean corpuscular hemoglobin), MCHC (mean corpuscular hemoglobin concentration)</p>