دورية أكاديمية
أعرض في EDS

γ-aminobutyric acid receptor B signaling drives glioblastoma in females in an immune-dependent manner.

التفاصيل البيبلوغرافية
العنوان: γ-aminobutyric acid receptor B signaling drives glioblastoma in females in an immune-dependent manner.
المؤلفون: Pathak A; Department of Molecular & Cellular Pharmacology, Leonard M. Miller School of Medicine, University of Miami, Miami, FL, USA.; Sylvester Comprehensive Cancer Center, University of Miami, Miami, FL, USA., Palasalava S; Department of Radiation Oncology, University of Michigan, Ann Arbor, MI, USA., Knott MV; Leonard M. Miller School of Medicine, University of Miami, Miami, FL, USA.; Department of Neurosurgery, Leonard M. Miller School of Medicine, University of Miami, Miami, FL., Colon B; Department of Molecular & Cellular Pharmacology, Leonard M. Miller School of Medicine, University of Miami, Miami, FL, USA., Ciervo E; Università degli Studi di Napoli Federico II, Napoli, ITALY., Zhou Y; Genomic Medicine Institute, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA., Mitchell J; Department of Molecular & Cellular Pharmacology, Leonard M. Miller School of Medicine, University of Miami, Miami, FL, USA.; Leonard M. Miller School of Medicine, University of Miami, Miami, FL, USA., Pumar OT; Department of Molecular & Cellular Pharmacology, Leonard M. Miller School of Medicine, University of Miami, Miami, FL, USA.; Sylvester Comprehensive Cancer Center, University of Miami, Miami, FL, USA., Wong HKA; Department of Molecular & Integrative Physiology, University of Michigan, Ann Arbor, MI, USA., Zhang L; Rogel Cancer Center, University of Michigan, Ann Arbor, MI, USA., Susic N; Leonard M. Miller School of Medicine, University of Miami, Miami, FL, USA., Shah KH; Leonard M. Miller School of Medicine, University of Miami, Miami, FL, USA., Kay K; Department of Cardiovascular & Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA., Chin D; Department of Cardiovascular & Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA., Johnson S; Department of Cardiovascular & Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA., Cheng F; Genomic Medicine Institute, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA.; Case Comprehensive Cancer Center, Cleveland, OH, USA., Lyssiotis CA; Rogel Cancer Center, University of Michigan, Ann Arbor, MI, USA., Watson DC; Sylvester Comprehensive Cancer Center, University of Miami, Miami, FL, USA.; Department of Molecular Oncology, Leonard M. Miller School of Medicine, University of Miami, Miami, FL., Ceccarelli M; Sylvester Comprehensive Cancer Center, University of Miami, Miami, FL, USA., Shah A; Sylvester Comprehensive Cancer Center, University of Miami, Miami, FL, USA.; Department of Neurosurgery, Leonard M. Miller School of Medicine, University of Miami, Miami, FL., Wahl DR; Department of Radiation Oncology, University of Michigan, Ann Arbor, MI, USA.; Rogel Cancer Center, University of Michigan, Ann Arbor, MI, USA., Lathia JD; Department of Cardiovascular & Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA.; Case Comprehensive Cancer Center, Cleveland, OH, USA.; Rose Ella Burkhardt Brain Tumor & Neuro-Oncology Center, Cleveland Clinic, Cleveland, OH, USA., Bayik D; Department of Molecular & Cellular Pharmacology, Leonard M. Miller School of Medicine, University of Miami, Miami, FL, USA.; Sylvester Comprehensive Cancer Center, University of Miami, Miami, FL, USA.
المصدر: BioRxiv : the preprint server for biology [bioRxiv] 2024 Jul 22. Date of Electronic Publication: 2024 Jul 22.
نوع المنشور: Journal Article; Preprint
اللغة: English
بيانات الدورية: Country of Publication: United States NLM ID: 101680187 Publication Model: Electronic Cited Medium: Internet ISSN: 2692-8205 (Electronic) Linking ISSN: 26928205 NLM ISO Abbreviation: bioRxiv Subsets: PubMed not MEDLINE
مستخلص: Sex differences in immune responses impact cancer outcomes and treatment response, including in glioblastoma (GBM). However, host factors underlying sex specific immune-cancer interactions are poorly understood. Here, we identify the neurotransmitter γ-aminobutyric acid (GABA) as a driver of GBM-promoting immune response in females. We demonstrated that GABA receptor B (GABBR) signaling enhances L-Arginine metabolism and nitric oxide synthase 2 (NOS2) expression in female granulocytic myeloid-derived suppressor cells (gMDSCs). GABBR agonist and GABA analog promoted GBM growth in females in an immune-dependent manner, while GABBR inhibition reduces gMDSC NOS2 production and extends survival only in females. Furthermore, female GBM patients have enriched GABA transcriptional signatures compared to males, and the use of GABA analogs in GBM patients is associated with worse short-term outcomes only in females. Collectively, these results highlight that GABA modulates anti-tumor immune response in a sex-specific manner, supporting future assessment of GABA pathway inhibitors as part of immunotherapy approaches.
Competing Interests: Conflict of interest: In the past three years, C.A.L. has consulted for Astellas Pharmaceuticals, Odyssey Therapeutics, Third Rock Ventures, and T-Knife Therapeutics, and is an inventor on patents pertaining to Kras regulated metabolic pathways, redox control pathways in pancreatic cancer, and targeting the GOT1-ME1 pathway as a therapeutic approach (US Patent No: 2015126580-A1, 05/07/2015; US Patent No: 20190136238, 05/09/2019; International Patent No: WO2013177426-A2, 04/23/2015). J.D.L reports being named as a co-inventor on pending and issued patents held by the Cleveland Clinic relating to cancer therapies, but these are not directly relevant to this work.
References: Nat Med. 2019 Mar;25(3):470-476. (PMID: 30742120)
Neuro Oncol. 2016 Sep;18(9):1253-64. (PMID: 27006175)
JCI Insight. 2017 Aug 3;2(15):. (PMID: 28768910)
Cancer Res. 2022 Nov 15;82(22):4274-4287. (PMID: 36126163)
Eur J Immunol. 2010 Dec;40(12):3347-57. (PMID: 21110318)
JCI Insight. 2018 Nov 2;3(21):. (PMID: 30385717)
Nature. 2021 Nov;599(7885):471-476. (PMID: 34732892)
J Natl Cancer Inst. 2021 Oct 1;113(10):1396-1404. (PMID: 33705549)
Cancers (Basel). 2023 Sep 06;15(18):. (PMID: 37760403)
Cell. 2023 Apr 13;186(8):1689-1707. (PMID: 37059069)
Science. 2013 Jul 12;341(6142):1236361. (PMID: 23846904)
Signal Transduct Target Ther. 2021 Jan 8;6(1):7. (PMID: 33414387)
Lancet Oncol. 2018 Aug;19(8):e379. (PMID: 30102229)
Eur J Neurosci. 2001 Oct;14(8):1294-302. (PMID: 11703458)
Cell. 2020 Apr 16;181(2):219-222. (PMID: 32302564)
Cancer Res. 2015 Dec 15;75(24):5273-82. (PMID: 26631269)
Oncogene. 2021 Feb;40(5):899-908. (PMID: 33288884)
Proc Natl Acad Sci U S A. 2014 Jan 21;111(3):984-9. (PMID: 24395782)
PLoS One. 2009 Jun 18;4(6):e5953. (PMID: 19536293)
Natl Sci Rev. 2020 Aug;7(8):1306-1318. (PMID: 34692159)
Immunol Invest. 2012;41(6-7):614-34. (PMID: 23017138)
J Control Release. 2024 May;369:199-214. (PMID: 38537717)
Nat Rev Drug Discov. 2019 Nov;18(12):899-900. (PMID: 31780841)
JAMA Oncol. 2020 Jul 1;6(7):1003-1010. (PMID: 32437507)
Cancer Discov. 2023 Sep 6;13(9):2090-2105. (PMID: 37378557)
Cancer Res. 2013 Nov 1;73(21):6413-23. (PMID: 24030977)
Front Immunol. 2022 May 31;13:887781. (PMID: 35711434)
Nat Rev Immunol. 2021 Aug;21(8):485-498. (PMID: 33526920)
Nat Med. 2019 Mar;25(3):477-486. (PMID: 30742122)
Nat Cell Biol. 2022 Feb;24(2):230-241. (PMID: 35145222)
Transl Cancer Res. 2021 Feb;10(2):637-644. (PMID: 35116397)
Int J Clin Pharm. 2022 Jun;44(3):689-697. (PMID: 35449347)
Cancer Cell. 2017 Mar 13;31(3):326-341. (PMID: 28292436)
Sci Adv. 2023 Jun 30;9(26):eadg3736. (PMID: 37390211)
Nat Metab. 2022 Oct;4(10):1322-1335. (PMID: 36192601)
Proc Natl Acad Sci U S A. 2016 Mar 15;113(11):3078-83. (PMID: 26929329)
Neuro Oncol. 2011 Jun;13(6):591-9. (PMID: 21636707)
Front Immunol. 2023 Jan 04;13:993444. (PMID: 36685592)
Metabolomics. 2022 Jan 6;18(1):9. (PMID: 34989902)
Nat Rev Cancer. 2016 May;16(5):330-9. (PMID: 27079803)
Oncoimmunology. 2016 Jun 27;5(8):e1200771. (PMID: 27622069)
Physiology (Bethesda). 2009 Jun;24:171-85. (PMID: 19509127)
Nature. 2019 Sep;573(7775):539-545. (PMID: 31534222)
Nat Rev Cancer. 2021 Jun;21(6):393-407. (PMID: 33879867)
Free Radic Biol Med. 2019 Jun;137:37-45. (PMID: 30991141)
Cancer Discov. 2020 Aug;10(8):1210-1225. (PMID: 32300059)
Oncogene. 2017 Feb 9;36(6):777-786. (PMID: 27375015)
Nature. 2023 May;617(7961):599-607. (PMID: 37138086)
Biol Sex Differ. 2020 Apr 15;11(1):17. (PMID: 32295632)
Am J Hosp Palliat Care. 2012 May;29(3):177-82. (PMID: 21745832)
BMC Cell Biol. 2012 Jul 04;13:18. (PMID: 22762146)
JAMA. 2017 Dec 19;318(23):2306-2316. (PMID: 29260225)
Cell. 2015 May 7;161(4):803-16. (PMID: 25913192)
Nat Neurosci. 2019 Aug;22(8):1289-1305. (PMID: 31285612)
Cancer Res. 2004 Aug 15;64(16):5839-49. (PMID: 15313928)
Nature. 2023 Jul;619(7971):844-850. (PMID: 37380778)
J Immunother Precis Oncol. 2024 May 2;7(2):97-110. (PMID: 38721406)
Sci Transl Med. 2023 Feb 8;15(682):eabn5649. (PMID: 36753564)
Antioxid Redox Signal. 2017 Jun 10;26(17):986-999. (PMID: 27411305)
Int J Cancer. 2014 Jun 15;134(12):2853-64. (PMID: 24259296)
Nat Commun. 2017 Apr 06;8:14979. (PMID: 28382931)
Front Immunol. 2017 Feb 07;8:93. (PMID: 28223985)
معلومات مُعتمدة: R00 CA248611 United States CA NCI NIH HHS; F31 CA264849 United States CA NCI NIH HHS; R37 CA258346 United States CA NCI NIH HHS; P50 CA269022 United States CA NCI NIH HHS; R01 NS129123 United States NS NINDS NIH HHS; R35 NS127083 United States NS NINDS NIH HHS; P01 CA245705 United States CA NCI NIH HHS; P30 CA240139 United States CA NCI NIH HHS; R00 CA277242 United States CA NCI NIH HHS; K08 CA234416 United States CA NCI NIH HHS
فهرسة مساهمة: Keywords: GABA; L-arginine; glioblastoma; myeloid-derived suppressor cells; nitric oxide synthase 2; sex differences
تواريخ الأحداث: Date Created: 20240802 Latest Revision: 20240809
رمز التحديث: 20240809
مُعرف محوري في PubMed: PMC11291093
DOI: 10.1101/2024.07.18.603996
PMID: 39091833
قاعدة البيانات: MEDLINE
الوصف
تدمد:2692-8205
DOI:10.1101/2024.07.18.603996