CoChat
Sign Up
Cited by 20Glioma Diagnosis and TreatmentCancer Immunotherapy and BiomarkersNeuroinflammation and Neurodegeneration Mechanisms

MR1 overexpression correlates with poor clinical prognosis in glioma patients

Open access
Kubica, Phillip, Lara-Velazquez, Montserrat, Bam, Marpe, Siraj, Seema, Ong, Irene, Liu, Peng, Priya, Raj, Salamat, Shahriar +2 more·2021·Neuro-Oncology Advances
DOI 10.1093/noajnl/vdab034PMC PMC8080245
Open this paper in CoChat — free accountOpen PDF

Abstract

Background: Glioblastoma is the most common adult primary brain tumor with near-universal fatality. Major histocompatibility complex (MHC) class I molecules are important mediators of CD8 activation and can be downregulated by cancer cells to escape immune surveillance. MR1 is a nonclassical MHC-I-like molecule responsible for the activation of a subset of T cells. Although high levels of MR1 expression should enhance cancer cell recognition, various tumors demonstrate MR1 overexpression with unknown implications. Here, we study the role of MR1 in glioma. Methods: Using multi-omics data from the Cancer Genome Atlas (TCGA), we studied MR1 expression patterns and its impact on survival for various solid tumors. In glioma specifically, we validated MR1 expression by histology, elucidate transcriptomic profiles of MR1 high versus low gliomas. To understand MR1 expression, we analyzed the methylation status of the MR1 gene and MR1 gene-related transcription factor (TF) expression. Results: MR1 is overexpressed in all grades of glioma and many other solid cancers. However, only in glioma, MR1 overexpression correlated with poor overall survival and demonstrated global dysregulation of many immune-related genes in an MR1-dependent manner. MR1 overexpression correlated with decreased MR1 gene methylation and upregulation of predicted MR1 promoter binding TFs, implying MR1 gene methylation might regulate MR1 expression in glioma. Conclusions: Our in silico analysis shows that MR1 expression is a predictor of clinical outcome in glioma patients and is potentially regulated at the epigenetic level, resulting in immune-related genes dysregulation. These findings need to be validated using independent in vitro and in vivo functional studies.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1093/noajnl/vdab034

Cites

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

No references could be resolved yet.

Research works printed but not linked: 45

  1. [1]Louis DN, Perry A, Reifenberger G, et al. The 2016 World Health Organization Classification of Tumors of the Central Nervous System: a summary. Acta Neuropathol. 2016; 131(6): 803– 820. 27157931
  2. [2]Stupp R, Mason WP, van den Bent MJ, et al.; European Organisation for Research and Treatment of Cancer Brain Tumor and Radiotherapy Groups; National Cancer Institute of Canada Clinical Trials Group. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med. 2005; 352(10): 987– 996. 15758009
  3. [3]Stupp R, Taillibert S, Kanner A, et al. Effect of tumor-treating fields plus maintenance temozolomide vs maintenance temozolomide alone on survival in patients with glioblastoma: a randomized clinical trial. JAMA. 2017; 318(23): 2306– 2316. 29260225 PMC5820703
  4. [4]Lara-Velazquez M, Al-Kharboosh R, Jeanneret S, et al. Advances in brain tumor surgery for glioblastoma in adults. Brain Sci. 2017; 7(12): 166. PMC5742769 29261148
  5. [5]Omuro A, DeAngelis LM. Glioblastoma and other malignant gliomas: a clinical review. JAMA. 2013; 310(17): 1842– 1850. 24193082
  6. [6]Chen Q, Han B, Meng X, et al. Immunogenomic analysis reveals LGALS1 contributes to the immune heterogeneity and immunosuppression in glioma. Int J Cancer. 2019; 145(2): 517– 530. 30613962
  7. [7]Pyaram K, Yadav VN. Advances in NKT cell immunotherapy for glioblastoma. J Cancer Sci Ther. 2018; 10(6): 533. 30147849 PMC6108592
  8. [8]Yang W, Li Y, Gao R, Xiu Z, Sun T. MHC class I dysfunction of glioma stem cells escapes from CTL-mediated immune response via activation of Wnt/β-catenin signaling pathway. Oncogene. 2020; 39(5): 1098– 1111. 31591480
  9. [9]Kamran N, Alghamri MS, Nunez FJ, et al. Current state and future prospects of immunotherapy for glioma. Immunotherapy. 2018; 10(4): 317– 339. 29421984 PMC5810852
  10. [10]Henriksen A, Dyhl-Polk A, Chen I, Nielsen D. Checkpoint inhibitors in pancreatic cancer. Cancer Treat Rev. 2019; 78: 17– 30. 31325788
  11. [11]Narayanan GA, Nellore A, Tran J, et al. Alternative splicing of MR1 regulates antigen presentation to MAIT cells. Sci Rep. 2020; 10(1): 15429. 32963314 PMC7508857
  12. [12]Lion J, Debuysscher V, Wlodarczyk A, et al. MR1B, a natural spliced isoform of the MHC-related 1 protein, is expressed as homodimers at the cell surface and activates MAIT cells. Eur J Immunol. 2013; 43(5): 1363– 1373. 23457030
  13. [13]Keller AN, Corbett AJ, Wubben JM, McCluskey J, Rossjohn J. MAIT cells and MR1-antigen recognition. Curr Opin Immunol. 2017; 46: 66– 74. 28494326
  14. [14]Mondot S, Boudinot P, Lantz O. MAIT, MR1, microbes and riboflavin: a paradigm for the co-evolution of invariant TCRs and restricting MHCI-like molecules? Immunogenetics. 2016; 68(8): 537– 548. 27393664
  15. [15]Park SJ, Yoon BH, Kim SK, Kim SY. GENT2: an updated gene expression database for normal and tumor tissues. BMC Med Genomics. 2019; 12(suppl 5): 101. 31296229 PMC6624177
  16. [16]Gupta S, Stamatoyannopoulos JA, Bailey TL, Noble WS. Quantifying similarity between motifs. Genome Biol. 2007; 8(2): R24. 17324271 PMC1852410
  17. [17]Yoshihama S, Vijayan S, Sidiq T, Kobayashi KS. NLRC5/CITA: a key player in cancer immune surveillance. Trends Cancer. 2017; 3(1): 28– 38. 28718425 PMC5518632
  18. [18]Kochan G, Escors D, Breckpot K, Guerrero-Setas D. Role of non-classical MHC class I molecules in cancer immunosuppression. Oncoimmunology. 2013; 2(11): e26491. 24482746 PMC3894240
  19. [19]Crowther MD, Dolton G, Legut M, et al. Genome-wide CRISPR-Cas9 screening reveals ubiquitous T cell cancer targeting via the monomorphic MHC class I-related protein MR1. Nat Immunol. 2020; 21(2): 178– 185. 31959982 PMC6983325
  20. [20]Yan J, Allen S, McDonald E, et al. MAIT cells promote tumor initiation, growth, and metastases via tumor MR1. Cancer Discov. 2020; 10(1): 124– 141. 31826876
  21. [21]Peterfalvi A, Gomori E, Magyarlaki T, et al. Invariant Valpha7.2-Jalpha33 TCR is expressed in human kidney and brain tumors indicating infiltration by mucosal-associated invariant T (MAIT) cells. Int Immunol. 2008; 20(12): 1517– 1525. 18927318
  22. [22]Won EJ, Ju JK, Cho YN, et al. Clinical relevance of circulating mucosal-associated invariant T cell levels and their anti-cancer activity in patients with mucosal-associated cancer. Oncotarget. 2016; 7(46): 76274– 76290. 27517754 PMC5342813
  23. [23]Liang L, Zeng M, Pan H, Liu H, He Y. Nicotinamide N-methyltransferase promotes epithelial-mesenchymal transition in gastric cancer cells by activating transforming growth factor-β1 expression. Oncol Lett. 2018; 15(4): 4592– 4598. 29541230 PMC5835905
  24. [24]Wu Y, Wu P, Zhang Q, Chen W, Liu X, Zheng W. MFAP5 promotes basal-like breast cancer progression by activating the EMT program. Cell Biosci. 2019; 9: 24. 30899449 PMC6407223
  25. [25]Tai CS, Lin YR, Teng TH, et al. Haptoglobin expression correlates with tumor differentiation and five-year overall survival rate in hepatocellular carcinoma. PLoS One. 2017; 12(2): e0171269. 28158312 PMC5291462
  26. [26]Zeng WJ, Yang YL, Wen ZP, Chen P, Chen XP, Gong ZC. Identification of gene expression and DNA methylation of SERPINA5 and TIMP1 as novel prognostic markers in lower-grade gliomas. Peerj. 2020; 8: e9262. 32547876 PMC7275683
  27. [27]Luo G, Zhou Y, Yi W, Yi H. Lactotransferrin expression is downregulated and affects the mitogen-activated protein kinase pathway in gastric cancer. Oncol Lett. 2015; 9(5): 2409– 2413. 26137081 PMC4467336
  28. [28]Dougherty GW, Mizuno K, Nöthe-Menchen T, et al. CFAP45 deficiency causes situs abnormalities and asthenospermia by disrupting an axonemal adenine nucleotide homeostasis module. Nat Commun. 2020; 11(1): 5520. 33139725 PMC7606486
  29. [29]Xu S, Zhao L, Larsson A, Venge P. The identification of a phospholipase B precursor in human neutrophils. FEBS J. 2009; 276(1): 175– 186. 19019078
  30. [30]Li B, Chen P, Wang J, et al. MicroRNA-1254 exerts oncogenic effects by directly targeting RASSF9 in human breast cancer. Int J Oncol. 2018; 53(5): 2145– 2156. 30132526
  31. [31]Stamatopoulos K, Belessi C, Hadzidimitriou A, et al. Immunoglobulin light chain repertoire in chronic lymphocytic leukemia. Blood. 2005; 106(10): 3575– 3583. 16076869
  32. [32]Qiu S, Pellino G, Fiorentino F, et al. A review of the role of neurotensin and its receptors in colorectal cancer. Gastroenterol Res Pract. 2017; 2017: 6456257. 28316623 PMC5339424
  33. [33]Chen JC, Cai HY, Wang Y, et al. Up-regulation of stomatin expression by hypoxia and glucocorticoid stabilizes membrane-associated actin in alveolar epithelial cells. J Cell Mol Med. 2013; 17(7): 863– 872. 23672602 PMC3822891
  34. [34]Crescioli S, Correa I, Karagiannis P, et al. IgG4 characteristics and functions in cancer immunity. Curr Allergy Asthma Rep. 2016; 16(1): 7. 26742760 PMC4705142
  35. [35]Kazanietz MG, Durando M, Cooke M. CXCL13 and its receptor CXCR5 in cancer: inflammation, immune response, and beyond. Front Endocrinol (Lausanne). 2019; 10: 471. 31354634 PMC6639976
  36. [36]Chang HJ, Yang MJ, Yang YH, Hou MF, Hsueh EJ, Lin SR. MMP13 is potentially a new tumor marker for breast cancer diagnosis. Oncol Rep. 2009; 22(5): 1119– 1127. 19787229
  37. [37]Liu Y, Wang Y, Sun X, et al. miR-449a promotes liver cancer cell apoptosis by downregulation of Calpain 6 and POU2F1. Oncotarget. 2016; 7(12): 13491– 13501. 26375440 PMC4924656
  38. [38]Shin H, Blackburn SD, Intlekofer AM, et al. A role for the transcriptional repressor Blimp-1 in CD8(+) T cell exhaustion during chronic viral infection. Immunity. 2009; 31(2): 309– 320. 19664943 PMC2747257
  39. [39]Fu SH, Yeh LT, Chu CC, Yen BL, Sytwu HK. New insights into Blimp-1 in T lymphocytes: a divergent regulator of cell destiny and effector function. J Biomed Sci. 2017; 24(1): 49. 28732506 PMC5520377
  40. [40]Wang D, Yang L, Yu W, et al. Colorectal cancer cell-derived CCL20 recruits regulatory T cells to promote chemoresistance via FOXO1/CEBPB/NF-κB signaling. J Immunother Cancer. 2019; 7(1): 215. 31395078 PMC6688336
  41. [41]Alsamman K, El-Masry OS. Interferon regulatory factor 1 inactivation in human cancer. Biosci Rep. 2018; 38(3). PMC5938431 29599126
  42. [42]Zhang R, Chen K, Peng L, Xiong H. Regulation of T helper cell differentiation by interferon regulatory factor family members. Immunol Res. 2012; 54(1–3): 169– 176. 22528124
  43. [43]Chiang HS, Liu HM. The molecular basis of viral inhibition of IRF- and STAT-dependent immune responses. Front Immunol. 2018; 9: 3086. 30671058 PMC6332930
  44. [44]Lepore M, Kalinichenko A, Calogero S, et al Functionally diverse human T cells recognize non-microbial antigens presented by MR1. Elife 2017; 18(6). PMC5459576 28518056
  45. [45]da Silva IL, Montero-Montero L, Ferreira E, Quintanilla M. New insights into the role of Qa-2 and HLA-G non-classical MHC-I complexes in malignancy. Front Immunol. 2018; 9: 2894. 30574154 PMC6292030

Cited by

Sorted by citations

Authors
Kubica, P., Lara-Velazquez, M., Bam, M., Siraj, S., Ong, I., Liu, P., Priya, R., Salamat, S., Brutkiewicz, R. R., & Dey, M.
Affiliations
  • University of Wisconsin–Madison (US)
  • Indiana University Indianapolis (US)
Corresponding author
Dey, Mahua
ORCID
Venue
Neuro-Oncology Advances
Publisher
Oxford University Press (OUP)
Published
2021-01-01
Volume
3
Issue
1
Pages
vdab034-vdab034
ISSN
2632-2498 (ISSN-L)
DOI
10.1093/noajnl/vdab034
PMC
PMC8080245
OpenAlex
W3131209553
Cited by
20
References
0
Citations by year
2026: 6 · 2025: 4 · 2024: 3 · 2023: 4 · 2022: 2 · 2021: 1
FWCI
1.40
Type
journal article
Language
en
Open access
Licence
Locations
  • Neuro-Oncology Advances (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • IUScholarWorks (Indiana University) (submittedVersion, cc-by)
Funders
National Institutes of Health (K08NS092895)
Topics
  • Health Sciences › Medicine › Genetics › Glioma Diagnosis and Treatment
  • Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Keywords
MR1, non-classical MHC class I, glioma, glioblastoma, prognostic factors, overall survival, DNA methylation, transcription factor binding, epigenetic regulation, tumor immune evasion, T cell activation

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review