Histologic characterization of the immune infiltrate in isocitrate dehydrogenase wild-type and mutant World Health Organization Grade II and III gliomas
Aim: This study aims to describe the immune infiltrations in low-grade glioma (LGG) with respect to their histological classification, isocitrate dehydrogenase 1 and 2 (IDH1/2) mutation status and survival. Materials and Methods: The IDH1/2 status (mutant or wild-type) of 66 World Health Organizatio...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Wolters Kluwer Medknow Publications
2018-01-01
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| Series: | Glioma |
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| Online Access: | http://www.jglioma.com/article.asp?issn=2589-6113;year=2018;volume=1;issue=6;spage=196;epage=200;aulast=Jansen |
| _version_ | 1830476460817645568 |
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| author | Josine A. E. M. Jansen Wim G. M. Spliet Wendy de Leng Pierre Alain Robe |
| author_facet | Josine A. E. M. Jansen Wim G. M. Spliet Wendy de Leng Pierre Alain Robe |
| author_sort | Josine A. E. M. Jansen |
| collection | DOAJ |
| description | Aim: This study aims to describe the immune infiltrations in low-grade glioma (LGG) with respect to their histological classification, isocitrate dehydrogenase 1 and 2 (IDH1/2) mutation status and survival. Materials and Methods: The IDH1/2 status (mutant or wild-type) of 66 World Health Organization Grade II and III gliomas were defined using next-generation sequencing or multiplex ligation-dependent probe amplification. The immune infiltrates of these tumors (46 mutant IDH, 20 wild-type IDH) were assessed immunohistochemically using a panel of antibodies (CD3, CD4, CD8, FOXP3, CD20, CD68, and CD163). Confirmatory analyses were performed on a cohort of lower grade gliomas from the Cancer Genome Atlas (TCGA). Statistical analyses were performed with Mann–Whitney U-tests and Kaplan–Meier survival estimates. Results: There was no relation between the amount of CD3+, CD4+, CD8+, or CD20+ lymphocyte infiltration and IDH mutation status in the tumors. FOXP3+ T regulatory cell infiltrates were rare, but more frequent in IDH1/2 wild-type tumors (P = 0.046). While the presence of these cells did not correlate with overall survival, FOXP3 messenger RNA expression was associated with survival in a distinct cohort of LGG from the TCGA (P < 0.05). CD4+ lymphocyte infiltrates, on the other hand, tended to prevail in astrocytic tumors as compared to oligodendrogliomas (P = 0.056). While CD68 (M1) microglial/monocytic cells were equally abundant in IDH mutant and wild-type tumors, the presence of round, activated M1 CD68+ microglia significantly associated with a mutant IDH status (P = 0.015). Conclusion: FOXP3+ expression and activated CD68+ M1 cells associated with IDH status in LGG, and might contribute to their differential evolution. |
| first_indexed | 2024-12-21T15:53:26Z |
| format | Article |
| id | doaj.art-e2d1651471304141b4b659ae5f1f40a1 |
| institution | Directory Open Access Journal |
| issn | 2589-6113 2589-6121 |
| language | English |
| last_indexed | 2024-12-21T15:53:26Z |
| publishDate | 2018-01-01 |
| publisher | Wolters Kluwer Medknow Publications |
| record_format | Article |
| series | Glioma |
| spelling | doaj.art-e2d1651471304141b4b659ae5f1f40a12022-12-21T18:58:10ZengWolters Kluwer Medknow PublicationsGlioma2589-61132589-61212018-01-011619620010.4103/glioma.glioma_42_18Histologic characterization of the immune infiltrate in isocitrate dehydrogenase wild-type and mutant World Health Organization Grade II and III gliomasJosine A. E. M. JansenWim G. M. SplietWendy de LengPierre Alain RobeAim: This study aims to describe the immune infiltrations in low-grade glioma (LGG) with respect to their histological classification, isocitrate dehydrogenase 1 and 2 (IDH1/2) mutation status and survival. Materials and Methods: The IDH1/2 status (mutant or wild-type) of 66 World Health Organization Grade II and III gliomas were defined using next-generation sequencing or multiplex ligation-dependent probe amplification. The immune infiltrates of these tumors (46 mutant IDH, 20 wild-type IDH) were assessed immunohistochemically using a panel of antibodies (CD3, CD4, CD8, FOXP3, CD20, CD68, and CD163). Confirmatory analyses were performed on a cohort of lower grade gliomas from the Cancer Genome Atlas (TCGA). Statistical analyses were performed with Mann–Whitney U-tests and Kaplan–Meier survival estimates. Results: There was no relation between the amount of CD3+, CD4+, CD8+, or CD20+ lymphocyte infiltration and IDH mutation status in the tumors. FOXP3+ T regulatory cell infiltrates were rare, but more frequent in IDH1/2 wild-type tumors (P = 0.046). While the presence of these cells did not correlate with overall survival, FOXP3 messenger RNA expression was associated with survival in a distinct cohort of LGG from the TCGA (P < 0.05). CD4+ lymphocyte infiltrates, on the other hand, tended to prevail in astrocytic tumors as compared to oligodendrogliomas (P = 0.056). While CD68 (M1) microglial/monocytic cells were equally abundant in IDH mutant and wild-type tumors, the presence of round, activated M1 CD68+ microglia significantly associated with a mutant IDH status (P = 0.015). Conclusion: FOXP3+ expression and activated CD68+ M1 cells associated with IDH status in LGG, and might contribute to their differential evolution.http://www.jglioma.com/article.asp?issn=2589-6113;year=2018;volume=1;issue=6;spage=196;epage=200;aulast=JansenImmune cell infiltrationisocitrate dehydrogenase mutationlow-grade gliomamicroglia |
| spellingShingle | Josine A. E. M. Jansen Wim G. M. Spliet Wendy de Leng Pierre Alain Robe Histologic characterization of the immune infiltrate in isocitrate dehydrogenase wild-type and mutant World Health Organization Grade II and III gliomas Glioma Immune cell infiltration isocitrate dehydrogenase mutation low-grade glioma microglia |
| title | Histologic characterization of the immune infiltrate in isocitrate dehydrogenase wild-type and mutant World Health Organization Grade II and III gliomas |
| title_full | Histologic characterization of the immune infiltrate in isocitrate dehydrogenase wild-type and mutant World Health Organization Grade II and III gliomas |
| title_fullStr | Histologic characterization of the immune infiltrate in isocitrate dehydrogenase wild-type and mutant World Health Organization Grade II and III gliomas |
| title_full_unstemmed | Histologic characterization of the immune infiltrate in isocitrate dehydrogenase wild-type and mutant World Health Organization Grade II and III gliomas |
| title_short | Histologic characterization of the immune infiltrate in isocitrate dehydrogenase wild-type and mutant World Health Organization Grade II and III gliomas |
| title_sort | histologic characterization of the immune infiltrate in isocitrate dehydrogenase wild type and mutant world health organization grade ii and iii gliomas |
| topic | Immune cell infiltration isocitrate dehydrogenase mutation low-grade glioma microglia |
| url | http://www.jglioma.com/article.asp?issn=2589-6113;year=2018;volume=1;issue=6;spage=196;epage=200;aulast=Jansen |
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