Clinicopathological correlation of tumor-associated macrophages in Ewing sarcoma

Abstract

Aims. Tumor-associated macrophages (TAMs) are known markers playing complex roles in tumorigenesis. However, the function of TAMs in a variety of malignancies is not yet fully understood. The aim of this pilot study was to quantify the density of TAMs in Ewing sarcoma and to determine the correlation between TAMs and clinicopathological parameters. Methods. Using immunohistochemistry, the expressions of CD68 and CD163 were examined in 24 tissue samples of Ewing sarcoma of bone. The density of CD68 and CD163-positive TAMs was analyzed quantitatively and semi-quantitatively and statistically correlated with clinical parameters. Results. CD163-positive TAMs outnumbered CD68-positive cells (median of 130 vs 96, respectively). No statistically significant relatio nship was found between density of CD68-positive cells, clinical parameters or prognosis. However, high levels of CD163-positive TAMs were associated with localized disease (P=0.008). In cases with a higher density of CD163-positive cells, a trend toward longer survival was revealed (P=0.063). Conclusion. This is the first study that has quantified CD163 expression in TAMs in Ewing sarcoma and showed its possible prognostic value. CD163 was confirmed to be a more specific marker of macrophages than CD68. CD163 is not an exclusive hallmark of M2 macrophages.

Comprehensive Analysis of Key Genes and Regulatory Elements in Ewing Sarcoma With Prognostic Values

“…A previous study revealed that BCL2 interacted with BCLXL to escape PARP inhibitor toxicity in ES [33]. The density of CD68-positive Tumor-associated macrophages was found in ES tissue samples and statistically correlated with clinical parameters [34]. Meanwhile, TEK and VEGFC were reported their expression was upregulated in ES which may allow the development of sarcoma subtype-targeted therapeutics [35,36].…”

Current Landscape of Immunotherapy for Advanced Sarcoma

“…Some studies suggest a positive impact of polarized macrophages with an M1 phenotype [ 74 ], but others have found no clear correlation with survival [ 75 ]. Some studies have even reported longer survival rates in osteosarcoma [ 76 ] and ES [ 77 ] patients with a high density of M2-like TAMs.…”

New Insights about the Wnt/β-Catenin Signaling Pathway in Primary Bone Tumors and Their Microenvironment: A Promising Target to Develop Therapeutic Strategies?

“…However, a recent study based on the most important cohort of osteosarcoma patients from the OS2006 clinical trial has demonstrated that the presence of CD163 + M2-polarized macrophages is crucial for the inhibition of osteosarcoma progression [35]. In contrast, macrophages do not seem to play such a role in Ewing sarcoma development and patient survival [39,40]. Moreover, M2-polarized macrophages contribute to the exhaustion of T lymphocytes infiltrating the tumor, reducing their proliferation and secretion of pro-inflammatory cytokines [41].…”

“…However, as described above, it remains difficult to conclude about the role of M2-polarized macrophages in osteosarcoma progression, probably because of the difficulty to clearly identify the different TAMs subtypes in tumors and by the fact that, in contrast to the binary M1/M2 subtype, TAMs correspond to several distinct populations that often share features of both subtypes [164]. In Ewing sarcoma, a first study has initially described a correlation between macrophages infiltrate and poor prognosis but a second one did not observe any correlation between CD68 + macrophages and survival [39,40]. The canonical Wnt/β-catenin signaling pathway seems to drive the polarization of macrophages in cancers.…”