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Tumor-associated Macrophage-derived Interleukin-23 Interlinks Kidney Cancer Glutamine Addiction with Immune Evasion

Glutamine addiction is a hallmark of clear cell renal cell carcinoma (ccRCC); yet whether glutamine metabolism impacts local immune surveillance is unclear. This knowledge may yield novel immunotherapeutic opportunities. To seek a potential therapeutic target in glutamine-addicted ccRCC. Tumors from...

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Bibliographic Details
Published in:European urology 2019-05, Vol.75 (5), p.752-763
Main Authors: Fu, Qiang, Xu, Le, Wang, Yiwei, Jiang, Qi, Liu, Zheng, Zhang, Junyu, Zhou, Quan, Zeng, Han, Tong, Shanyou, Wang, Tao, Qi, Yangyang, Hu, Baoying, Fu, Hangcheng, Xie, Huyang, Zhou, Lin, Chang, Yuan, Zhu, Yu, Dai, Bo, Zhang, Weijuan, Xu, Jiejie
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Language:English
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Summary:Glutamine addiction is a hallmark of clear cell renal cell carcinoma (ccRCC); yet whether glutamine metabolism impacts local immune surveillance is unclear. This knowledge may yield novel immunotherapeutic opportunities. To seek a potential therapeutic target in glutamine-addicted ccRCC. Tumors from ccRCC patients from a Shanghai cohort and ccRCC tumor data from The Cancer Genome Atlas (TCGA) cohort were analyzed. In vivo and in vitro studies were conducted with fresh human ccRCC tumors and murine tumor cells. Immune cell numbers and functions were analyzed by flow cytometry. Glutamine and cytokine concentrations were determined. Survival was compared between different subpopulations of patients using Kaplan-Meier and Cox regression analyses. We found that in ccRCC, high interleukin (IL)-23 expression was significantly associated with poor survival in both TCGA (overall survival [OS] hazard ratio [HR]=2.04, cancer-specific survival [CSS] HR=2.95; all p
ISSN:0302-2838
1873-7560
DOI:10.1016/j.eururo.2018.09.030