title: Clinical significance of CD163⁺ tumor-associated macrophages in patients with adult T-cell leukemia/lymphoma.
abstract: In several malignant tumors including lymphoma, macrophages that infiltrate tumor tissues are called tumor-associated macrophages (TAMs). We discovered that TAMs, especially the CD163⁺ alternatively activated phenotype (M2), were closely involved with progression of adult T-cell leukemia/lymphoma (ATLL). We used CD68 (a pan-macrophage marker) and CD163 (an M2 marker) to immunostain 58 ATLL samples. Statistical analyses showed that a high number of CD68⁺ TAMs and an increased percentage of CD163⁺ cells among the TAMs were associated with a worse clinical prognosis; multivariate analysis indicated that the percentage of CD163⁺ cells was an independent prognostic factor. We also carried out in vitro coculture experiments with ATLL cell lines (ATN-1 and TL-Mor) and monocyte-derived macrophages and found that direct coculture with M2 macrophages significantly increased BrdU incorporation into ATLL cell lines. A cytokine array analysis showed that macrophage-derived soluble factors including C5a, tumor necrosis factor-α, growth-related oncogene-α, CCL1/I-309, and interleukin-6 stimulated ATLL cell lines. CD163 expression in macrophages was strongly induced by direct contact with ATN-1 cells, and downregulation of CD163 in macrophages significantly suppressed growth of cocultured ATN-1 cells. These results suggest that interaction between M2 macrophages and lymphoma cells may be an appropriate target in treatment of patients with ATLL.
authors.affiliation: Department of Cell Pathology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan. ycomo@kumamoto-u.ac.jp
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Komohara
authors.forename: Daisuke
authors.initials: D
authors.lastname: Niino
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Saito
authors.forename: Koji
authors.initials: K
authors.lastname: Ohnishi
authors.forename: Hasita
authors.initials: H
authors.lastname: Horlad
authors.forename: Koichi
authors.initials: K
authors.lastname: Ohshima
authors.forename: Motohiro
authors.initials: M
authors.lastname: Takeya
mesh_terms: D000368:Aged; D015703:Antigens, CD / Q000276:immunology / Q000378:metabolism*; D015214:Antigens, Differentiation, Myelomonocytic / Q000276:immunology / Q000378:metabolism*; D045744:Cell Line, Tumor; D054402:Chemokine CCL1 / Q000378:metabolism; D054360:Chemokine CXCL1 / Q000378:metabolism; D015936:Complement C5a / Q000276:immunology / Q000378:metabolism; D018450:Disease Progression; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000276:immunology / Q000378:metabolism* / Q000473:pathology*; D008264:Macrophages / Q000276:immunology / Q000378:metabolism*; D008297:Male; D011379:Prognosis; D011956:Receptors, Cell Surface / Q000276:immunology / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D000098902:CD163 Antigen; D000097382:CD68 Molecule
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D054402:Chemokine CCL1; D054360:Chemokine CXCL1; D015936:Complement C5a; D015850:Interleukin-6; D011956:Receptors, Cell Surface; D014409:Tumor Necrosis Factor-alpha; D000098902:CD163 Antigen; C065971:CCL1 protein, human; C067980:CD68 antigen, human; D000097382:CD68 Molecule; C508600:IL6 protein, human
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