Targeting glutamine metabolism as an effective means to promote allograft acceptance while inhibit tumor growth.

Recently the role of metabolic signaling pathways has emerged as playing a critical role in dictating the outcome of T cell responses. The uptake and metabolism of the amino acid glutamine is essential for effector T cell activation. Since the growth and expansion of tumor cells relies on similar anabolic and metabolic requirements, we hypothesized that glutamine blockage might represent a promising strategy to promote allograft survival while inhibit tumor growth. 6-Diazo-5-oxo-L-norleucine (DON) was used as a glutamine antagonist. First, an in vitro study of T cell proliferation was performed to examine the ability of glutamine antagonism to inhibit T cell proliferation. Then we investigated whether DON could prolong allograft survival and inhibit tumor growth by using a fully MHC-mismatched mice full thickness skin transplantation model and a mice TC-1 tumor-bearing model. The proliferation study demonstrated that DON inhibited effector T cells proliferation in a dose-dependent manner. We found a marked prolonged graft median survival time and significant tumor inhibition for mice that received DON compared to those that received no treatment. These results highlight that targeting glutamine metabolism can promote allograft acceptance in a long tumor-free period. Copyright © 2020 Elsevier B.V. All rights reserved.

Citation

Chen-Fang Lee, Chih-Hsien Cheng, Hao-Chien Hung, Kun-Ming Chan, Wei-Chen Lee. Targeting glutamine metabolism as an effective means to promote allograft acceptance while inhibit tumor growth. Transplant immunology. 2020 Dec;63:101336

Mesh Tags

Substances

PMID: 32937197

search → result