@article{7ee777a7796e481dbcfae18678383376,
title = "Targeting glutamine metabolism enhances tumor-specific immunity by modulating suppressive myeloid cells",
abstract = "Myeloid cells comprise a major component of the tumor microenvironment (TME) that promotes tumor growth and immune evasion. By employing a small-molecule inhibitor of glutamine metabolism, not only were we able to inhibit tumor growth, but we markedly inhibited the generation and recruitment of myeloid-derived suppressor cells (MDSCs). Targeting tumor glutamine metabolism led to a decrease in CSF3 and hence recruitment of MDSCs as well as immunogenic cell death, leading to an increase in inflammatory tumor-associated macrophages (TAMs). Alternatively, inhibiting glutamine metabolism of the MDSCs themselves led to activation-induced cell death and conversion of MDSCs to inflammatory macrophages. Surprisingly, blocking glutamine metabolism also inhibited IDO expression of both the tumor and myeloid-derived cells, leading to a marked decrease in kynurenine levels. This in turn inhibited the development of metastasis and further enhanced antitumor immunity. Indeed, targeting glutamine metabolism rendered checkpoint blockade-resistant tumors susceptible to immunotherapy. Overall, our studies define an intimate interplay between the unique metabolism of tumors and the metabolism of suppressive immune cells.",
author = "Oh, {Min Hee} and Sun, {Im Hong} and Liang Zhao and Leone, {Robert D.} and Sun, {Im Meng} and Wei Xu and Collins, {Samuel L.} and Tam, {Ada J.} and Blosser, {Richard L.} and Patel, {Chirag H.} and Englert, {Judson M.} and Arwood, {Matthew L.} and Jiayu Wen and Yee Chan-Li and Luk{\'a}{\v s} Tenora and Pavel Majer and Rana Rais and Slusher, {Barbara S.} and Horton, {Maureen R.} and Powell, {Jonathan D.}",
note = "Funding Information: We thank the members of the Horton and Powell labs for review of this manuscript, and we thank T.C. Wu for his gift of mice. This work was supported by NIH grants R01CA229451 to JDP and BSS, R01HL141490 to MRH, and grants R01AI077610, R01CA226765, P41EB028239, and Cancer Center Core grant P30CA006973 to JDP; Bloomberg~Kimmel Institute for Cancer Immunotherapy funds to JDP and BSS, as well as Under Armour Women's Health and Breast Cancer Innovation grants to JDP. Funding Information: We thank the members of the Horton and Powell labs for review of this manuscript, and we thank T.C. Wu for his gift of mice. This work was supported by NIH grants R01CA229451 to JDP and BSS, R01HL141490 to MRH, and grants R01AI077610, R01CA226765, P41EB028239, and Cancer Center Core grant P30CA006973 to JDP; Bloomberg~Kimmel Institute for Cancer Immunotherapy funds to JDP and BSS, as well as Under Armour Women{\textquoteright}s Health and Breast Cancer Innovation grants to JDP. Publisher Copyright: Copyright: {\textcopyright} 2020, American Society for Clinical Investigation.",
year = "2020",
month = jul,
day = "1",
doi = "10.1172/JCI131859",
language = "English (US)",
volume = "130",
pages = "3865--3884",
journal = "Journal of Clinical Investigation",
issn = "0021-9738",
publisher = "The American Society for Clinical Investigation",
number = "7",
}