Abstract
AbstractNeuroblastoma (NB) is the most common extracranial solid tumor and the treatment efficacy of high-risk NB is unsatisfactory. γδT-cell-based adoptive cell transfer is a promising approach for high-risk NB treatment. Our previous study has revealed that γδT cells in NB patients exhibit a poor proliferation activity and a decreased anti-tumor capacity in vitro. In the present study, we found that IL-15 could effectively enhance the proliferation of NB γδT cells, to a level that remains lower than healthy controls though. In addition, IL-15-fostered NB γδT cells robustly boosted cell survival against apoptosis induced by cytokines depletion. Our data revealed that Mcl-1 was a key anti-apoptotic protein in IL-15-fostered γδT cells during cytokine withdrawal and its expression was regulated via the activation of STAT5 and ERK. In addition, IL-2 and IL-15-fostered γδT cells harbored higher levels of tumoricidal capacity which is also beneficial for γδ T-cell based immune therapy in NB. Understanding the survival control of γδT cells in a sub-optimal cytokine supportive microenvironment will expedite the clinical application of γδT cells for immunotherapy.
Funder
National Natural Science Foundation of China
Publisher
Springer Science and Business Media LLC
Subject
Cancer Research,Cell Biology,Cellular and Molecular Neuroscience,Immunology
Cited by
2 articles.
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