The cryo-thermal therapy-induced IL-6-rich acute pro-inflammatory response promoted DCs phenotypic maturation as the prerequisite to CD4<sup>+</sup> T cell differentiation

<p>In our previous studies, a novel tumour therapeutic modality of the cryo-thermal therapy has been developed leading to long-term survival in 4T1 murine mammary carcinoma model. The cryo-thermal therapy induced the strong acute inflammatory response and IL-6 was identified in an acute profile. In this study, we found that the cryo-thermal therapy triggered robust acute inflammatory response with high expression of IL-6 locally and systemically. The phenotypic maturation of dendritic cells (DCs) was induced by acute IL-6 following the treatment. The mature DCs promoted CD4<sup>+</sup> T cell differentiation. Moreover, the production of interferon γ (IFN γ) in the serum and CD4<sup>+</sup> T cells were both abrogated by IL-6 neutralisation following the treatment. Our findings revealed that the cryo-thermal therapy-induced acute IL-6 played an important role in initiating the cascading innate and adaptive anti-tumour immune responses, resulting in CD4<sup>+</sup> T cell differentiation. It would be interesting to investigate acute IL-6 as an early indicator in predicating tumour therapeutic effect.</p>