IMMU-91. Ligand receptor analyses of glioma immune microenvironment identifies Galectin-9 in microglia as regulator of tumor cell adhesion and phagocytosis Article Swipe
Pravesh Gupta
,
Silvana Valdebenito-Silva
,
Gayatri Kumar
,
Prashanth Chakrapani
,
Shivangi Oberai
,
Minghao Dang
,
Karen Clise-Dwyer
,
Linghua Wang
,
Eliseo A. Eugenín
,
Krishna Bhat
·
YOU?
·
· 2025
· Open Access
·
· DOI: https://doi.org/10.1093/neuonc/noaf201.0889
YOU?
·
· 2025
· Open Access
·
· DOI: https://doi.org/10.1093/neuonc/noaf201.0889
Innate immune cells of macrophage family predominate tumor immune microenvironment of CNS malignancies. Although macrophages exhibit myriads of protective functions such as clearance of malignant cells, immune surveillance, inflammation resolution and tissue repair, they are generally linked to immunosuppression in gliomas. To identify anti-glioma myeloid cell effectors, we performed directionally concatenated ligand-receptor (L-R) interactome analyses from dendritic cells (DC) and microglia (MG) to lymphoid (CD4+T, Tregs, CD8+T, NK and NKT) cells identified by single cell transcriptomics analyses of ~145,000 tumor-associated CD45+ leukocytes from tumor brains of eighteen high-grade and low-grade glioma patients. Amongst DC-specific (e.g. adhesion molecules) and MG-specific (e.g. chemokine family) interactomes, we identified LGALS9 encoding Galectin-9 as the most pertinent interactions (e.g. SORL1 encoding sortilin-related receptor 1) in MG of IDH-wild type gliomas. Spectral cytometry, immunohistochemistry and western blotting analyses of MG, macrophage, DC, lymphoid cells and tumor cells confirmed abundant expression of Galectin-9 in glioma-associated MG and not in Nestin+ tumor cells. Furthermore, differential gene enrichment analyses revealed transcripts associated with cellular adhesion (coronin 1A, integrin) and phagocytosis (FcγR, phospholipase D, Rab family proteins etc.) was significantly upregulated in Galectin-9hi compared to Galectin-9lo/- MG and macrophages predicting putative role of Galectin-9 in tumor cell adhesion and phagocytosis. Using glioblastoma relevant patient derived ex vivo primary microglia (pMGs; 707, 2103, 1805) and glioma stem cell (GSC) co-culture model system, we evaluated the functional role of Galectin-9. Confocal imaging analyses of co-cultured pMGs with GSC revealed that siRNA or neutralizing antibody mediated downregulation of Galectin-9 led to significantly impaired adhesion (p<0.001) between pMGs and GSC. Not only adhesion but even phagocytosis of GSC was dramatically attenuated (p<0.0001) across all Galectin-9 silenced or neutralized pMGs. Altogether, our study underscores unappreciated role of Galectin-9 in MG as regulator of glioma cell adhesion and phagocytosis that can be harnessed for glioblastoma immunotherapy.
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- article
- Language
- en
- Landing Page
- https://doi.org/10.1093/neuonc/noaf201.0889
- https://academic.oup.com/neuro-oncology/article-pdf/27/Supplement_5/v224/65255577/noaf201.0889.pdf
- OA Status
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- OpenAlex ID
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Raw OpenAlex JSON
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https://openalex.org/W4416085060Canonical identifier for this work in OpenAlex
- DOI
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https://doi.org/10.1093/neuonc/noaf201.0889Digital Object Identifier
- Title
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IMMU-91. Ligand receptor analyses of glioma immune microenvironment identifies Galectin-9 in microglia as regulator of tumor cell adhesion and phagocytosisWork title
- Type
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articleOpenAlex work type
- Language
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enPrimary language
- Publication year
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2025Year of publication
- Publication date
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2025-11-01Full publication date if available
- Authors
-
Pravesh Gupta, Silvana Valdebenito-Silva, Gayatri Kumar, Prashanth Chakrapani, Shivangi Oberai, Minghao Dang, Karen Clise-Dwyer, Linghua Wang, Eliseo A. Eugenín, Krishna BhatList of authors in order
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https://doi.org/10.1093/neuonc/noaf201.0889Publisher landing page
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https://academic.oup.com/neuro-oncology/article-pdf/27/Supplement_5/v224/65255577/noaf201.0889.pdfDirect link to full text PDF
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YesWhether a free full text is available
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bronzeOpen access status per OpenAlex
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https://academic.oup.com/neuro-oncology/article-pdf/27/Supplement_5/v224/65255577/noaf201.0889.pdfDirect OA link when available
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| abstract_inverted_index.as | 22, 109, 286 |
| abstract_inverted_index.be | 296 |
| abstract_inverted_index.by | 73 |
| abstract_inverted_index.ex | 206 |
| abstract_inverted_index.in | 40, 120, 147, 152, 182, 195, 284 |
| abstract_inverted_index.of | 4, 11, 18, 24, 78, 86, 122, 133, 145, 193, 227, 232, 245, 263, 282, 288 |
| abstract_inverted_index.or | 240, 273 |
| abstract_inverted_index.to | 38, 63, 185, 248 |
| abstract_inverted_index.we | 48, 104, 222 |
| abstract_inverted_index.1A, | 168 |
| abstract_inverted_index.CNS | 12 |
| abstract_inverted_index.DC, | 136 |
| abstract_inverted_index.GSC | 236, 264 |
| abstract_inverted_index.MG, | 134 |
| abstract_inverted_index.Not | 257 |
| abstract_inverted_index.Rab | 175 |
| abstract_inverted_index.all | 270 |
| abstract_inverted_index.and | 31, 60, 69, 89, 98, 129, 139, 150, 170, 188, 199, 214, 255, 292 |
| abstract_inverted_index.are | 35 |
| abstract_inverted_index.but | 260 |
| abstract_inverted_index.can | 295 |
| abstract_inverted_index.for | 298 |
| abstract_inverted_index.led | 247 |
| abstract_inverted_index.not | 151 |
| abstract_inverted_index.our | 277 |
| abstract_inverted_index.the | 110, 224 |
| abstract_inverted_index.was | 179, 265 |
| abstract_inverted_index.(DC) | 59 |
| abstract_inverted_index.(MG) | 62 |
| abstract_inverted_index.707, | 211 |
| abstract_inverted_index.GSC. | 256 |
| abstract_inverted_index.NKT) | 70 |
| abstract_inverted_index.cell | 46, 75, 197, 217, 290 |
| abstract_inverted_index.even | 261 |
| abstract_inverted_index.from | 56, 83 |
| abstract_inverted_index.gene | 158 |
| abstract_inverted_index.most | 111 |
| abstract_inverted_index.only | 258 |
| abstract_inverted_index.pMGs | 234, 254 |
| abstract_inverted_index.role | 192, 226, 281 |
| abstract_inverted_index.stem | 216 |
| abstract_inverted_index.such | 21 |
| abstract_inverted_index.that | 238, 294 |
| abstract_inverted_index.they | 34 |
| abstract_inverted_index.type | 124 |
| abstract_inverted_index.vivo | 207 |
| abstract_inverted_index.with | 164, 235 |
| abstract_inverted_index.(GSC) | 218 |
| abstract_inverted_index.(L-R) | 53 |
| abstract_inverted_index.(e.g. | 95, 100, 114 |
| abstract_inverted_index.1805) | 213 |
| abstract_inverted_index.2103, | 212 |
| abstract_inverted_index.CD45+ | 81 |
| abstract_inverted_index.SORL1 | 115 |
| abstract_inverted_index.Using | 201 |
| abstract_inverted_index.cells | 3, 58, 71, 138, 141 |
| abstract_inverted_index.etc.) | 178 |
| abstract_inverted_index.model | 220 |
| abstract_inverted_index.pMGs. | 275 |
| abstract_inverted_index.siRNA | 239 |
| abstract_inverted_index.study | 278 |
| abstract_inverted_index.tumor | 8, 84, 140, 154, 196 |
| abstract_inverted_index.(pMGs; | 210 |
| abstract_inverted_index.CD8+T, | 67 |
| abstract_inverted_index.Innate | 1 |
| abstract_inverted_index.LGALS9 | 106 |
| abstract_inverted_index.Tregs, | 66 |
| abstract_inverted_index.across | 269 |
| abstract_inverted_index.brains | 85 |
| abstract_inverted_index.cells, | 26 |
| abstract_inverted_index.cells. | 155 |
| abstract_inverted_index.family | 6, 176 |
| abstract_inverted_index.glioma | 91, 215, 289 |
| abstract_inverted_index.immune | 2, 9, 27 |
| abstract_inverted_index.linked | 37 |
| abstract_inverted_index.single | 74 |
| abstract_inverted_index.tissue | 32 |
| abstract_inverted_index.(CD4+T, | 65 |
| abstract_inverted_index.(FcγR, | 172 |
| abstract_inverted_index.Amongst | 93 |
| abstract_inverted_index.Nestin+ | 153 |
| abstract_inverted_index.between | 253 |
| abstract_inverted_index.derived | 205 |
| abstract_inverted_index.exhibit | 16 |
| abstract_inverted_index.family) | 102 |
| abstract_inverted_index.imaging | 230 |
| abstract_inverted_index.myeloid | 45 |
| abstract_inverted_index.myriads | 17 |
| abstract_inverted_index.patient | 204 |
| abstract_inverted_index.primary | 208 |
| abstract_inverted_index.repair, | 33 |
| abstract_inverted_index.system, | 221 |
| abstract_inverted_index.western | 130 |
| abstract_inverted_index.(coronin | 167 |
| abstract_inverted_index.Abstract | 0 |
| abstract_inverted_index.Although | 14 |
| abstract_inverted_index.Confocal | 229 |
| abstract_inverted_index.IDH-wild | 123 |
| abstract_inverted_index.Spectral | 126 |
| abstract_inverted_index.abundant | 143 |
| abstract_inverted_index.adhesion | 96, 166, 198, 251, 259, 291 |
| abstract_inverted_index.analyses | 55, 77, 132, 160, 231 |
| abstract_inverted_index.antibody | 242 |
| abstract_inverted_index.blotting | 131 |
| abstract_inverted_index.cellular | 165 |
| abstract_inverted_index.compared | 184 |
| abstract_inverted_index.eighteen | 87 |
| abstract_inverted_index.encoding | 107, 116 |
| abstract_inverted_index.gliomas. | 41, 125 |
| abstract_inverted_index.identify | 43 |
| abstract_inverted_index.impaired | 250 |
| abstract_inverted_index.lymphoid | 64, 137 |
| abstract_inverted_index.mediated | 243 |
| abstract_inverted_index.proteins | 177 |
| abstract_inverted_index.putative | 191 |
| abstract_inverted_index.receptor | 118 |
| abstract_inverted_index.relevant | 203 |
| abstract_inverted_index.revealed | 161, 237 |
| abstract_inverted_index.silenced | 272 |
| abstract_inverted_index.~145,000 | 79 |
| abstract_inverted_index.chemokine | 101 |
| abstract_inverted_index.clearance | 23 |
| abstract_inverted_index.confirmed | 142 |
| abstract_inverted_index.dendritic | 57 |
| abstract_inverted_index.evaluated | 223 |
| abstract_inverted_index.functions | 20 |
| abstract_inverted_index.generally | 36 |
| abstract_inverted_index.harnessed | 297 |
| abstract_inverted_index.integrin) | 169 |
| abstract_inverted_index.low-grade | 90 |
| abstract_inverted_index.malignant | 25 |
| abstract_inverted_index.microglia | 61, 209 |
| abstract_inverted_index.patients. | 92 |
| abstract_inverted_index.performed | 49 |
| abstract_inverted_index.pertinent | 112 |
| abstract_inverted_index.regulator | 287 |
| abstract_inverted_index.Galectin-9 | 108, 146, 194, 246, 271, 283 |
| abstract_inverted_index.associated | 163 |
| abstract_inverted_index.attenuated | 267 |
| abstract_inverted_index.co-culture | 219 |
| abstract_inverted_index.cytometry, | 127 |
| abstract_inverted_index.effectors, | 47 |
| abstract_inverted_index.enrichment | 159 |
| abstract_inverted_index.expression | 144 |
| abstract_inverted_index.functional | 225 |
| abstract_inverted_index.high-grade | 88 |
| abstract_inverted_index.identified | 72, 105 |
| abstract_inverted_index.leukocytes | 82 |
| abstract_inverted_index.macrophage | 5 |
| abstract_inverted_index.molecules) | 97 |
| abstract_inverted_index.predicting | 190 |
| abstract_inverted_index.protective | 19 |
| abstract_inverted_index.resolution | 30 |
| abstract_inverted_index.Altogether, | 276 |
| abstract_inverted_index.DC-specific | 94 |
| abstract_inverted_index.Galectin-9. | 228 |
| abstract_inverted_index.MG-specific | 99 |
| abstract_inverted_index.anti-glioma | 44 |
| abstract_inverted_index.co-cultured | 233 |
| abstract_inverted_index.interactome | 54 |
| abstract_inverted_index.macrophage, | 135 |
| abstract_inverted_index.macrophages | 15, 189 |
| abstract_inverted_index.neutralized | 274 |
| abstract_inverted_index.predominate | 7 |
| abstract_inverted_index.transcripts | 162 |
| abstract_inverted_index.underscores | 279 |
| abstract_inverted_index.upregulated | 181 |
| abstract_inverted_index.Furthermore, | 156 |
| abstract_inverted_index.Galectin-9hi | 183 |
| abstract_inverted_index.concatenated | 51 |
| abstract_inverted_index.differential | 157 |
| abstract_inverted_index.dramatically | 266 |
| abstract_inverted_index.glioblastoma | 202, 299 |
| abstract_inverted_index.inflammation | 29 |
| abstract_inverted_index.interactions | 113 |
| abstract_inverted_index.neutralizing | 241 |
| abstract_inverted_index.phagocytosis | 171, 262, 293 |
| abstract_inverted_index.directionally | 50 |
| abstract_inverted_index.interactomes, | 103 |
| abstract_inverted_index.malignancies. | 13 |
| abstract_inverted_index.phagocytosis. | 200 |
| abstract_inverted_index.phospholipase | 173 |
| abstract_inverted_index.significantly | 180, 249 |
| abstract_inverted_index.surveillance, | 28 |
| abstract_inverted_index.unappreciated | 280 |
| abstract_inverted_index.Galectin-9lo/- | 186 |
| abstract_inverted_index.downregulation | 244 |
| abstract_inverted_index.immunotherapy. | 300 |
| abstract_inverted_index.ligand-receptor | 52 |
| abstract_inverted_index.transcriptomics | 76 |
| abstract_inverted_index.(p&lt;0.001) | 252 |
| abstract_inverted_index.microenvironment | 10 |
| abstract_inverted_index.sortilin-related | 117 |
| abstract_inverted_index.tumor-associated | 80 |
| abstract_inverted_index.(p&lt;0.0001) | 268 |
| abstract_inverted_index.glioma-associated | 148 |
| abstract_inverted_index.immunosuppression | 39 |
| abstract_inverted_index.immunohistochemistry | 128 |
| cited_by_percentile_year | |
| countries_distinct_count | 1 |
| institutions_distinct_count | 10 |
| citation_normalized_percentile |