PMID- 23741072 OWN - NLM STAT- MEDLINE DCOM- 20140205 LR - 20220330 IS - 1557-3265 (Electronic) IS - 1078-0432 (Linking) VI - 19 IP - 14 DP - 2013 Jul 15 TI - Glioma grade is associated with the accumulation and activity of cells bearing M2 monocyte markers. PG - 3776-86 LID - 10.1158/1078-0432.CCR-12-1940 [doi] AB - PURPOSE: This study is directed at identifying the cell source(s) of immunomodulatory cytokines in high-grade gliomas and establishing whether the analysis of associated markers has implications for tumor grading. EXPERIMENTAL DESIGN: Glioma specimens classified as WHO grade II-IV by histopathology were assessed by gene expression analysis and immunohistochemistry to identify the cells producing interleukin (IL)-10, which was confirmed by flow cytometry and factor secretion in culture. Finally, principal component analysis (PCA) and mixture discriminant analysis (MDA) were used to investigate associations between expressed genes and glioma grade. RESULTS: The principle source of glioma-associated IL-10 is a cell type that bears phenotype markers consistent with M2 monocytes but does not express all M2-associated genes. Measures of expression of the M2 cell markers CD14, CD68, CD163, and CD204, which are elevated in high-grade gliomas, and the neutrophil/myeloid-derived suppressor cell (MDSC) subset marker CD15, which is reduced, provide the best index of glioma grade. CONCLUSIONS: Grade II and IV astrocytomas can be clearly differentiated on the basis of the expression of certain M2 markers in tumor tissues, whereas grade III astrocytomas exhibit a range of expression between the lower and higher grade specimens. The content of CD163(+) cells distinguishes grade III astrocytoma subsets with different prognosis. FAU - Prosniak, Michael AU - Prosniak M AD - Department of Cancer Biology, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA. FAU - Harshyne, Larry A AU - Harshyne LA FAU - Andrews, David W AU - Andrews DW FAU - Kenyon, Lawrence C AU - Kenyon LC FAU - Bedelbaeva, Kamila AU - Bedelbaeva K FAU - Apanasovich, Tatiyana V AU - Apanasovich TV FAU - Heber-Katz, Ellen AU - Heber-Katz E FAU - Curtis, Mark T AU - Curtis MT FAU - Cotzia, Paolo AU - Cotzia P FAU - Hooper, D Craig AU - Hooper DC LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20130605 PL - United States TA - Clin Cancer Res JT - Clinical cancer research : an official journal of the American Association for Cancer Research JID - 9502500 RN - 0 (Antigens, CD) RN - 0 (Antigens, Differentiation, Myelomonocytic) RN - 0 (Biomarkers, Tumor) RN - 0 (CD163 antigen) RN - 0 (IL10 protein, human) RN - 0 (Immunologic Factors) RN - 0 (Receptors, Cell Surface) RN - 0 (Transforming Growth Factor beta) RN - 130068-27-8 (Interleukin-10) SB - IM MH - Adult MH - Aged MH - Antigens, CD/metabolism MH - Antigens, Differentiation, Myelomonocytic/metabolism MH - Biomarkers, Tumor/*metabolism MH - Brain Neoplasms/immunology/*metabolism/mortality/pathology MH - Female MH - Gene Expression MH - Glioblastoma/immunology/*metabolism/mortality/pathology MH - Humans MH - Immunologic Factors/genetics/metabolism MH - Interleukin-10/genetics/metabolism MH - Kaplan-Meier Estimate MH - Macrophages/*metabolism MH - Male MH - Microglia/metabolism MH - Middle Aged MH - Neoplasm Grading MH - Phenotype MH - Receptors, Cell Surface/metabolism MH - Transforming Growth Factor beta/genetics/metabolism EDAT- 2013/06/07 06:00 MHDA- 2014/02/06 06:00 CRDT- 2013/06/07 06:00 PHST- 2013/06/07 06:00 [entrez] PHST- 2013/06/07 06:00 [pubmed] PHST- 2014/02/06 06:00 [medline] AID - 1078-0432.CCR-12-1940 [pii] AID - 10.1158/1078-0432.CCR-12-1940 [doi] PST - ppublish SO - Clin Cancer Res. 2013 Jul 15;19(14):3776-86. doi: 10.1158/1078-0432.CCR-12-1940. Epub 2013 Jun 5.