短暂 40 °C 热休克通过上调 HSP70 增强 Vδ2(+) γδ T 细胞的细胞毒性反应

Vδ2 + γδ T cell, one of promising strategies for tumor immunotherapy, recognizes and kills cancer cells in a non-MHC dependent manner. Previously, we pioneeringly proved the clinical safety and efficacy of allogeneic Vδ2 + γδ T cells, in vitro expanded from healthy donors, in the treatment of late-stage cancer patients. Nevertheless, how to profoundly potentiate cytotoxic function of expanded Vδ2 + γδ T cells remains to be further explored.

Here, we proposed that 40 °C-Shock could be a simple and reliable approach to in vitro boost the effector function.

We found that 40 °C-shock could phosphorylate two MAPK proteins ERK and p38 through HSP70, which facilitated actyl-α-tubulin and actin augments and reorganization, elevated Ki-67 expression and cell surface adhesion, and promoted releases of cytokines IFN-γ, perforin and granzyme B, as well as downregulated LAG3 expression.

We also observed 40 °C-shock induced elevations of mitochondrial metabolism. These altogether led to potentiated cytotoxic responses against cancer cells. This proof-of-concept work demonstrated that 40 °C-shock would be probably developed into an effective method to in vitro boost the cytotoxicity of Vδ2 + γδ T cell before applying it in immunotherapy, and provided scientific evidences for the view that fever can activate immune responses of innate immune cells.