Pan-cancer analysis of B3GNT5 with potential implications for cancer immunotherapy and cancer stem cell stemness.

Publisher: Public Library of Science Country of Publication: United States NLM ID: 101285081 Publication Model: eCollection Cited Medium: Internet ISSN: 1932-6203 (Electronic) Linking ISSN: 19326203 NLM ISO Abbreviation: PLoS One Subsets: MEDLINE

Original Publication: San Francisco, CA : Public Library of Science

Immunotherapy*/methods ; Neoplastic Stem Cells*/metabolism ; Neoplastic Stem Cells*/pathology ; Neoplastic Stem Cells*/immunology ; N-Acetylglucosaminyltransferases*/metabolism ; N-Acetylglucosaminyltransferases*/genetics; Humans ; Animals ; Mice ; Cell Line, Tumor ; Gene Expression Regulation, Neoplastic ; Neoplasms/immunology ; Neoplasms/therapy ; Neoplasms/pathology ; Neoplasms/genetics ; Prognosis ; T-Lymphocytes/immunology ; T-Lymphocytes/metabolism ; Pancreatic Neoplasms/immunology ; Pancreatic Neoplasms/pathology ; Pancreatic Neoplasms/genetics ; Pancreatic Neoplasms/therapy

B3GNT5, a critical member of the β-1,3-N-acetylglucosaminyl transferase gene family involved in lactose and glycosphingolipids biosynthesis, has been documented to promote tumor-infiltrating T-cell responses. Our research utilized the Pan-Cancer dataset from The Cancer Genome Atlas (TCGA) to explore the functional role of B3GNT5. Our study demonstrated that the antibody-driven inhibition of B3GNT5 diminished T cell-mediated anti-tumor responses in both in vitro and in vivo settings. By analyzing RNA-seq data from Genotype-Tissue Expression (GTEx) and TCGA databases, we observed differential expression levels of B3GNT5 across various tumor types accompanied by an unfavorable prognostic correlation. We further utilized integrated clinical survival data from TCGA and immune cell infiltration scoring patterns to identify significant associations between B3GNT5 expression and immune checkpoints, cancer stemness, chemokines, chemokine receptors, and immune-activating genes. B3GNT5's expression was highly correlated with different immunoregulatory factors, including T cell infiltration, chemokine receptors, and activation genes. Subsequent experiments discovered that suppressing B3GNT5 expression in pancreatic adenocarcinoma cells significantly reduced their tumorigenicity by limiting sphere-forming ability and self-renewal capacity, thus underscoring B3GNT5's vital role as a prognostic factor in immune regulation across pan-cancer. Our findings suggest that B3GNT5 presents a viable target for cancer immunotherapy by enabling effective communication between cancer stem cells and immune cells during tumor treatment.
Competing Interests: The authors have declared that no competing interests exist
(Copyright: © 2024 Peng et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Cancer Res. 2015 May 15;75(10):2095-108. (PMID: 25808872)
Cell Death Dis. 2018 Feb 14;9(2):249. (PMID: 29445149)
Immunol Rev. 2021 Mar;300(1):100-124. (PMID: 33682165)
Front Immunol. 2020 Feb 05;11:140. (PMID: 32117287)
Nature. 2009 Nov 26;462(7272):510-3. (PMID: 19898495)
Nat Rev Clin Oncol. 2019 Jun;16(6):356-371. (PMID: 30705439)
J Biol Chem. 1993 Oct 15;268(29):21727-33. (PMID: 8408027)
Cell Metab. 2021 May 4;33(5):1001-1012.e5. (PMID: 33691090)
CA Cancer J Clin. 2015 Mar;65(2):87-108. (PMID: 25651787)
Int J Radiat Biol. 2019 Feb;95(2):144-155. (PMID: 30395764)
J Biol Chem. 1998 Apr 3;273(14):8508-15. (PMID: 9525965)
Immunity. 2021 Jan 12;54(1):132-150.e9. (PMID: 33271119)
J Exp Med. 2008 Jul 7;205(7):1635-46. (PMID: 18591411)
Cell Rep. 2021 Jan 5;34(1):108597. (PMID: 33406434)
Inflammopharmacology. 2018 May 7;:. (PMID: 29736687)
Cell Immunol. 2005 Dec;238(2):67-75. (PMID: 16574086)
Stem Cells. 2017 Dec;35(12):2351-2365. (PMID: 29044882)
Chem Rev. 2018 Sep 12;118(17):8188-8241. (PMID: 29979587)
Mol Cancer Ther. 2010 Jan;9(1):67-78. (PMID: 20053772)
Proc Natl Acad Sci U S A. 2010 Jun 29;107(26):11900-5. (PMID: 20547865)
Science. 2008 Jan 11;319(5860):198-202. (PMID: 18187654)
Clin Proteomics. 2017 May 23;14:20. (PMID: 28546799)
Annu Rev Immunol. 2001;19:375-96. (PMID: 11244041)
FEBS J. 2016 Jul;283(14):2731-48. (PMID: 26787424)
Glycobiology. 2012 Jul;22(7):930-8. (PMID: 22411838)
Front Immunol. 2021 Jul 09;12:688215. (PMID: 34305920)
Blood. 2007 May 1;109(9):3776-85. (PMID: 17218381)
Proc Natl Acad Sci U S A. 2019 Apr 30;116(18):9020-9029. (PMID: 30996127)
Clin Exp Immunol. 2018 Jan;191(1):60-73. (PMID: 28868628)
Br J Cancer. 2014 Oct 14;111(8):1634-45. (PMID: 25167227)
Front Oncol. 2021 Jul 12;11:636365. (PMID: 34322374)
Curr Opin Immunol. 2006 Jun;18(3):298-304. (PMID: 16603343)
Curr Opin Immunol. 2006 Jun;18(3):286-91. (PMID: 16616474)
FEBS Lett. 2010 May 3;584(9):1901-6. (PMID: 19874824)
Leukemia. 2022 Feb;36(2):403-415. (PMID: 34381181)
CNS Neurosci Ther. 2020 Nov;26(11):1147-1154. (PMID: 32677340)
Nat Immunol. 2008 May;9(5):503-10. (PMID: 18425107)
Immunol Rev. 2008 Jun;223:284-99. (PMID: 18613843)
Cancer Cell. 2017 Jun 12;31(6):848-848.e1. (PMID: 28609660)
Cancer Res. 2019 Jul 15;79(14):3737-3748. (PMID: 31085700)

EC 2.4.1.- (N-Acetylglucosaminyltransferases)

Date Created: 20241213 Date Completed: 20241213 Latest Revision: 20241215

20250114

PMC11642946

10.1371/journal.pone.0314609

39671359