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-a, growth-related oncogene-a, 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. (Cancer Sci 2013; 104: 945-951)

Endogenous dendritic cells from the tumor microenvironment support T-ALL growth via IGF1R activation

“…These findings suggest that Sirpα + DCs are most capable of supporting T-ALL growth, although our data demonstrate that other myeloid cells likely contribute. Similarly, monocytes differentiated into M2 macrophages were shown to directly promote proliferation of adult T-cell leukemia/lymphoma cell lines (52). Thus, it will be important to evaluate the respective roles of tumor-associated Sirpα + and Sirpα − DCs, as well as other myeloid subsets in supporting T-ALL growth.…”

Microenvironment of adult T-cell leukemia/lymphoma-associated nodal lesions

“…In addition, the number of CD68-positive macrophages in ATLL tissues did not correlate with overall survival (P = 0.25), whereas patients with a large number of CD163-positive macrophages (C250 cells/mm 2 tumor area; n = 37) had worse outcomes than those with a small number (\250 cells/mm 2 tumor area; n = 36) (P = 0.05). Moreover, a higher ratio of CD163-positive to CD68-positive macrophages in ATLL significantly correlated with worse overall survival (P = 0.039), while multivariate analysis demonstrated that the number of CD163-positive macrophages constitutes an independent prognostic factor [24].…”

TIM-3 expression in lymphoma cells predicts chemoresistance in patients with adult T-cell leukemia/lymphoma

“…The experimental procedure was approved by the Kumamoto University Review Board (Kumamoto, Japan). We previously published characteristics of this same set of ATLL specimens, and thus, the numbers of CD68-and CD163-positive cells published in that previous report (11) were used in this study.…”

“…We previously demonstrated that macrophages induced ATLL cell proliferation and that a higher density of tumor-associated macrophages (TAMs) in ATLL tissues was closely associated with a poor clinical prognosis (11). It was also found that direct contact with macrophages induced ATLL cell activation, although the detailed mechanisms have not yet been elucidated (11).…”

“…It was also found that direct contact with macrophages induced ATLL cell activation, although the detailed mechanisms have not yet been elucidated (11).…”