A24 Session 7: Advances in Thermal Medicine

It is becoming increasingly clear that tumor control by standard chemotherapy and radiotherapy as well as high- and low-temperature ablative modalities depend on the CD8 T cell-mediated adaptive immune response. Unfortunately, in many cases the ability of these therapies to activate the endogenous CD8 T cell response is not sufficient to induce durable protection from tumor outgrowth. Here, we report on recent findings suggesting that the local inflammatory response generated as a consequence of two thermal therapy modalities, i.e., mild-temperature systemic thermal therapy (core temperature elevated to ∼39.5°C, for 6h; STT) or RFA (90°C, 1min), provides a favorable environment for immune intervention in tumor progression when combined with an active immunotherapy regimen. These studies employed adoptive T cell transfer immunotherapy after thermal to investigate immune-mediated tumor control in murine tumor models. Mice implanted subcutaneously with B16 melanoma or CT26 colorectal tumors were pre-treated with thermal therapy followed by adoptive transfer of tumor-antigen specific CD8 effector T cells. A key endpoint was the assessment of T cell trafficking to lymph nodes (LNs) and tumors which are the respective initiation and effector sites of antitumor immunity. Strong induction of naïve CD8 T cell trafficking was detected in LNs after administration of STT. STT also elevated trafficking of tumor-specific CD8 effector T cells across the normally recalcitrant tumor vessels. Enhanced CD8 effector T cell recruitment in tumors was linked to increased antigen-restricted apoptosis of tumor cell targets and improved overall survival. Recent results comparing the immunomodulatory activities of STT and RFA will also be discussed. Collectively, our studies suggest that thermal therapy has clinical potential as an adjuvant therapy to augment the efficacy of cancer immunotherapy.Supported by grants from the NIH (CA79765 and AI082039).