RRC ID 44376
Author Komohara Y, Niino D, Saito Y, Ohnishi K, Horlad H, Ohshima K, Takeya M.
Title Clinical significance of CD163⁺ tumor-associated macrophages in patients with adult T-cell leukemia/lymphoma.
Journal Cancer Sci
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.
Volume 104(7)
Pages 945-51
Published 2013-7-1
DOI 10.1111/cas.12167
PMID 23557330
PMC PMC7657152
MeSH Aged Antigens, CD / immunology Antigens, CD / metabolism* Antigens, Differentiation, Myelomonocytic / immunology Antigens, Differentiation, Myelomonocytic / metabolism* Cell Line, Tumor Chemokine CCL1 / metabolism Chemokine CXCL1 / metabolism Complement C5a / immunology Complement C5a / metabolism Disease Progression Female Humans Interleukin-6 / metabolism Leukemia-Lymphoma, Adult T-Cell / immunology Leukemia-Lymphoma, Adult T-Cell / metabolism* Leukemia-Lymphoma, Adult T-Cell / pathology* Macrophages / immunology Macrophages / metabolism* Male Prognosis Receptors, Cell Surface / immunology Receptors, Cell Surface / metabolism* Tumor Necrosis Factor-alpha / metabolism
IF 4.966
Times Cited 60
Human and Animal Cells ATN-1(RCB1440) TL-Mor(RCB1881)