Transient 40 °C-shock potentiates cytotoxic responses of Vδ2+ γδ T cell via HSP70 upregulation.
Cancer Immunol Immunother
; 71(10): 2391-2404, 2022 Oct.
Article
en En
| MEDLINE
| ID: mdl-35195762
ABSTRACT
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.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Linfocitos T
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Proteínas HSP70 de Choque Térmico
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Linfocitos Intraepiteliales
Límite:
Humans
Idioma:
En
Revista:
Cancer Immunol Immunother
Asunto de la revista:
ALERGIA E IMUNOLOGIA
/
NEOPLASIAS
/
TERAPEUTICA
Año:
2022
Tipo del documento:
Article