Prognostic significance of CD68, CD163 and Folate receptor‑β positive macrophages in hepatocellular carcinoma

Abstract

Cluster of differentiation (CD)68 may be used as a pan-macrophage or M1 marker, whereas CD163 may be used as an M2 marker. Furthermore, folate receptor (FR)β exhibits an M2-like functional profile. In the present study, CD68 and CD163 were used to evaluate and classify tumor-associated macrophages (TAMs). The expression of CD68, CD163 and FRβ by TAMs in hepatocellular carcinoma (HCC) Tissues was investigated. Samples from 105 patients with HCC were evaluated using immunohistochemistry. The results revealed that CD68 and CD163 overexpression was associated with a worse prognosis. The number of CD68 positive cells observed was significantly higher in patients with stage IV cancer. Furthermore, an increase in CD68 positive cells was observed in patients with median tumor size ≥3.5 cm and in patients with poorly differentiated HCC. The number of CD163 positive cells was also significantly increased in patients with median tumor size ≥3.5 cm and in those with poorly differentiated HCC. A low CD163/68 ratio was correlated with a worse outcome. The ratio was significantly lower in patients with stage IV cancer, patients with des-gamma-carboxy prothrombin abnormalities, patients with blood vessel infiltration and patients with intrahepatic metastasis. The number of FRβ positive cells was not correlated with clinicopathological features. The results of the present study indicate that overexpression of CD68 and CD163 may be associated with a worse patient outcome. The evaluation of CD68 and CD163 positive cells in a cancer microenvironment is controversial. TAMs are not simply cells with single markers or restricted M1 or M2 phenotypes; they are more diverse and heterogeneous. Further studies are required to determine the cross-interaction between diverse TAMs and the tumor microenvironment.

Pathologic assessment of tumor-associated macrophages and their histologic localization in invasive breast carcinoma

“…Several markers are used to label macrophages. CD68 identifies ER estrogen receptor, PR progesterone receptor *Statistically significant both tumoricidal M1 and tumor-promoting M2 macrophages, whereas CD163 is expressed principally by M2 macrophages [16]. Studies investigated TAMs infiltration within BC were remarkably variable.…”

Targeting folate receptor β positive tumor-associated macrophages in lung cancer with a folate-modified liposomal complex

“…FRα and FRβ, which are attached to the cell membrane through glycosylphosphatidylinositol (GPI) anchors, are overexpressed in tumor cells and TAMs, respectively. [7][8][9][10][11] FRγ is secreted from tissues of hematopoietic origin due to the lack of an efficient signal for GPI modification and has a much lower affinity for folate than FRα and FRβ. [12][13][14] FRδ has proven elusive in human tissues, suggesting that it is highly restricted both spatially and temporally.…”

Nanoparticle-based targeted delivery of pentagalloyl glucose reverses elastase-induced abdominal aortic aneurysm and restores aorta to the healthy state in mice

“…In our study, we found a significant amount of CD 68 (M1 type macrophage) and activated macrophage Mac-2 in PPE treated aorta. Macrophages rapidly secrete a wide range of inflammatory mediators such as IL-13, IL-6, and TNFα and overexpression of these inflammatory mediators is reported in experimental AAA followed by the infiltration of monocytes, neutrophils and lymphocytes and then followed by VSMCs apoptosis 19,4 . Others have shown that apoptosis in VSMCs releases MMPs, which degrade ECM leading to vessel damage 30 .…”

“…Immunofluorescence staining was conducted for CD 68 cells, which is also known as pan-macrophage and is regarded as M1 macrophage marker 19 . We observed that after the treatment with PGG, CD 68 positive cells significantly decreased in the aneurysmal aorta in comparison to PPE treated aorta ( Figure 7A).…”