Macrophage Densities Correlated with CXC Chemokine Receptor 4 Expression and Related with Poor Survival in Anaplastic Thyroid Cancer

Abstract

BackgroundTumor associated macrophages (TAMs) and CXC chemokine receptor 4 (CXCR4) have emerged as potential biomarkers in various human cancers. The aims of this study were to investigate the clinical characteristics of anaplastic thyroid cancer (ATC) patients according to the TAM numbers in the tumor tissue, and to evaluate the associations between CXCR4 expressions and macrophage densities in ATC tumor microenvironment.MethodsTotal 14 ATC samples from thyroid tissue microarray were used. Immunohistochemical staining was performed using anti-CD163 and anti-CXCR4 antibodies. According to the immunoreactivity of CD163, all subjects were divided into two groups: low-CD163 (n=8) and high-CD163 (n=6) groups.ResultsThe mean diagnostic age was 65±7 years and the median tumor size was 4.3 cm, ranging 2.5 to 15 cm. Clinicopathological characteristics were not significantly different between low-CD163 and high-CD163 groups, while age of diagnosis was younger in high-CD163 group than that of low-CD163 group with marginal significance (56.9±5.5 years vs. 67.5±6.8 years, P=0.09). However, overall survival was significantly reduced in high-CD163 group (5.5 months [range, 1 to 10]) compared with low-CD163 groups (8.8 months [range, 6 to 121); log-rank test, P=0.0443). Moreover, high-CD163 group showed strong CXCR4 expressions in both cancer and stromal compartments, while low-CD163 group showed relatively weak, stromal-dominant CXCR4 expressions. Additionally, CD163 and CXCR4 expressions showed a strong positive correlation (γ2=0.432, P=0.013).ConclusionIncreased number of TAMs showed poor overall survival in ATC, suggesting TAMs are potentially a prognostic biomarker for ATC. CXCR4 expression was significantly correlated with CD163-positive TAM densities, which suggest the possible role of CXCR4 in TAM recruitments.

Low Lymphocyte-to-Monocyte Ratios Are Associated with Poor Overall Survival in Anaplastic Thyroid Carcinoma Patients

“…In a previous study, the coexistence of lymphocytic thyroiditis was significantly associated with favorable outcomes in papillary thyroid cancer (14). Furthermore, increased TAM infiltration is reportedly associated with poor survival of patients with anaplastic thyroid carcinoma (ATC), the most fatal form of thyroid cancer (15)(16)(17)(18)(19). These studies suggest the important role of the immune system in the progression of thyroid cancer.…”

Role of chemokine receptors in thyroid cancer and immunotherapy

“…CXCL4, CXCL9-10-11 Normal human thyroid cells, human TPC-1 cell line, non-metastatic human PTC (Urra et al 2018) No data available No data available CXCR4 CXCL12 Normal human thyroid cells (González et al 2009), rat RET/PTC thyroid cancer cell line (Castellone et al 2004), human PTC, human ATC, human MTC, human FTC, human ARO cells (He et al 2010, Torregrossa et al 2010, 2012, Shin et al 2013 TAM (Kim et al 2016) Promotion of rat thyroid cancer cell migration (Castellone et al 2004) Promotion of in vitro human anaplastic thyroid cell migration, Association with human metastasis in vivo (Torregrossa et al 2010(Torregrossa et al , 2012) Promotion of EMT (Hwang et al 2003) CXCR7…”

“…It seems worth highlighting that the expression of CXCR4 also influences cell traffic in thyroid cancer microenvironment. Indeed, in anaplastic thyroid cancer (ATC) a significant correlation between CXCR4 expression and numbers of tumorassociated macrophages (TAMs) was reported (Kim et al 2016). CXCL12 induced migration in human thyroid anaplastic carcinoma cell lines (ARO), which was inhibited by an anti-CXCR4 antibody (Hwang et al 2003).…”

Exosomes derived from retinoblastoma cells enhance tumour deterioration by infiltrating the microenvironment

“…It was found that miRNAs (miR-92a, miR-20a, miR-129 and miR-17), CXCR4 and TSP-1 were detectable in EXOs derived from retinoblastoma cells. According to previous studies, miRNAs (miR-92a, miR-20a, miR-129 and miR-17), CXCR4 and TSP-1 are involved in TAM recruitment and proliferation (45)(46)(47)(48)(49)(50)(51). For example, miR-92a stimulates the secretion of the proinflammatory cytokine IL-6 in TAMs, which in turn promotes tumour cell proliferation, invasion and metastasis by interacting with the surrounding microenvironment (46).…”

“…However, of note, TSP-1 was detected in EXOs. CXCR4 and TSP-1 are involved in proliferation and TAM recruitment (45)(46)(47)(48)(49)(50)(51). Thus, the contents of EXOs may play a key role in EXO-mediated tumour progression.…”