Elucidating Immunometabolic Targets in Glioblastoma

Overview

Journal Am J Cancer Res

Specialty Oncology

Date 2017 Nov 10

PMID 29119048

Citations 3

Authors

Pooja Agarwal

Michael J Pajor

David M Anson

Maheedhara R Guda

Collin M Labak

Andrew J Tsung

Kiran K Velpula

Affiliations

Soon will be listed here.

Abstract

Immunometabolism has recently emerged on the forefront of cancer research as a new avenue to potentially develop more effective and targeted treatment options. Several pathologically altered metabolic targets across various cancer types have been identified, including lactate in aerobic glycolysis; tryptophan in amino acid metabolism; and arginine in the urea cycle. Numerous advancements have improved our understanding of the dual function of these targets in influencing immune functions as an auxiliary function to their well-established metabolic role. This paper provides a comprehensive overview of immunometabolism research and attempts to provide insight into potential immunometabolic targets in glioblastoma for the purpose of future development and study of targeted therapies.

Citing Articles

Pharmacotherapeutic Treatment of Glioblastoma: Where Are We to Date?.

Gatto L, Di Nunno V, Franceschi E, Tosoni A, Bartolini S, Brandes A Drugs. 2022; 82(5):491-510.

PMID: 35397073 DOI: 10.1007/s40265-022-01702-6.

The versatile role of HuR in Glioblastoma and its potential as a therapeutic target for a multi-pronged attack.

Guha A, Waris S, Nabors L, Filippova N, Gorospe M, Kwan T Adv Drug Deliv Rev. 2021; 181:114082.

PMID: 34923029 PMC: 8916685. DOI: 10.1016/j.addr.2021.114082.

Metabolic Drivers of Invasion in Glioblastoma.

Garcia J, Jain S, Aghi M Front Cell Dev Biol. 2021; 9:683276.

PMID: 34277624 PMC: 8281286. DOI: 10.3389/fcell.2021.683276.

References

Velpula K, Bhasin A, Asuthkar S, Tsung A . Combined targeting of PDK1 and EGFR triggers regression of glioblastoma by reversing the Warburg effect. Cancer Res. 2013; 73(24):7277-89. DOI: 10.1158/0008-5472.CAN-13-1868. View

Wainwright D, Balyasnikova I, Chang A, Ahmed A, Moon K, Auffinger B . IDO expression in brain tumors increases the recruitment of regulatory T cells and negatively impacts survival. Clin Cancer Res. 2012; 18(22):6110-21. PMC: 3500434. DOI: 10.1158/1078-0432.CCR-12-2130. View

Uyttenhove C, Pilotte L, Theate I, Stroobant V, Colau D, Parmentier N . Evidence for a tumoral immune resistance mechanism based on tryptophan degradation by indoleamine 2,3-dioxygenase. Nat Med. 2003; 9(10):1269-74. DOI: 10.1038/nm934. View

Daniele S, Giacomelli C, Zappelli E, Granchi C, Trincavelli M, Minutolo F . Lactate dehydrogenase-A inhibition induces human glioblastoma multiforme stem cell differentiation and death. Sci Rep. 2015; 5:15556. PMC: 4616042. DOI: 10.1038/srep15556. View

Rath M, Muller I, Kropf P, Closs E, Munder M . Metabolism via Arginase or Nitric Oxide Synthase: Two Competing Arginine Pathways in Macrophages. Front Immunol. 2014; 5:532. PMC: 4209874. DOI: 10.3389/fimmu.2014.00532. View

Shevach E . Fatal attraction: tumors beckon regulatory T cells. Nat Med. 2004; 10(9):900-1. DOI: 10.1038/nm0904-900. View

Romano A, Parrinello N, Vetro C, Tibullo D, Giallongo C, La Cava P . The prognostic value of the myeloid-mediated immunosuppression marker Arginase-1 in classic Hodgkin lymphoma. Oncotarget. 2016; 7(41):67333-67346. PMC: 5341879. DOI: 10.18632/oncotarget.12024. View

Ostrom Q, Gittleman H, Fulop J, Liu M, Blanda R, Kromer C . CBTRUS Statistical Report: Primary Brain and Central Nervous System Tumors Diagnosed in the United States in 2008-2012. Neuro Oncol. 2015; 17 Suppl 4:iv1-iv62. PMC: 4623240. DOI: 10.1093/neuonc/nov189. View

DeBerardinis R . Is cancer a disease of abnormal cellular metabolism? New angles on an old idea. Genet Med. 2008; 10(11):767-77. PMC: 2782690. DOI: 10.1097/GIM.0b013e31818b0d9b. View

10.

Geiger R, Rieckmann J, Wolf T, Basso C, Feng Y, Fuhrer T . L-Arginine Modulates T Cell Metabolism and Enhances Survival and Anti-tumor Activity. Cell. 2016; 167(3):829-842.e13. PMC: 5075284. DOI: 10.1016/j.cell.2016.09.031. View

11.

Cao Y, Feng Y, Zhang Y, Zhu X, Jin F . L-Arginine supplementation inhibits the growth of breast cancer by enhancing innate and adaptive immune responses mediated by suppression of MDSCs in vivo. BMC Cancer. 2016; 16:343. PMC: 4888479. DOI: 10.1186/s12885-016-2376-0. View

12.

Friedman M, McELIN T . Diagnosis of ruptured fetal membranes. Clinical study and review of the literature. Am J Obstet Gynecol. 1969; 104(4):544-50. DOI: 10.1016/s0002-9378(16)34244-2. View

13.

Platten M, Wick W, Van den Eynde B . Tryptophan catabolism in cancer: beyond IDO and tryptophan depletion. Cancer Res. 2012; 72(21):5435-40. DOI: 10.1158/0008-5472.CAN-12-0569. View

14.

Godin-Ethier J, Hanafi L, Piccirillo C, Lapointe R . Indoleamine 2,3-dioxygenase expression in human cancers: clinical and immunologic perspectives. Clin Cancer Res. 2011; 17(22):6985-91. DOI: 10.1158/1078-0432.CCR-11-1331. View

15.

Woehrer A, Bauchet L, Barnholtz-Sloan J . Glioblastoma survival: has it improved? Evidence from population-based studies. Curr Opin Neurol. 2014; 27(6):666-74. DOI: 10.1097/WCO.0000000000000144. View

16.

Mondanelli G, Bianchi R, Pallotta M, Orabona C, Albini E, Iacono A . A Relay Pathway between Arginine and Tryptophan Metabolism Confers Immunosuppressive Properties on Dendritic Cells. Immunity. 2017; 46(2):233-244. PMC: 5337620. DOI: 10.1016/j.immuni.2017.01.005. View

17.

Husain Z, Huang Y, Seth P, Sukhatme V . Tumor-derived lactate modifies antitumor immune response: effect on myeloid-derived suppressor cells and NK cells. J Immunol. 2013; 191(3):1486-95. DOI: 10.4049/jimmunol.1202702. View

18.

Shime H, Yabu M, Akazawa T, Kodama K, Matsumoto M, Seya T . Tumor-secreted lactic acid promotes IL-23/IL-17 proinflammatory pathway. J Immunol. 2008; 180(11):7175-83. DOI: 10.4049/jimmunol.180.11.7175. View

19.

Mitsuka K, Kawataki T, Satoh E, Asahara T, Horikoshi T, Kinouchi H . Expression of indoleamine 2,3-dioxygenase and correlation with pathological malignancy in gliomas. Neurosurgery. 2013; 72(6):1031-8. DOI: 10.1227/NEU.0b013e31828cf945. View

20.

Meissner M, Reichert T, Kunkel M, Gooding W, Whiteside T, Ferrone S . Defects in the human leukocyte antigen class I antigen processing machinery in head and neck squamous cell carcinoma: association with clinical outcome. Clin Cancer Res. 2005; 11(7):2552-60. DOI: 10.1158/1078-0432.CCR-04-2146. View