Potential role of tumor‐associated macrophages and CD163/CD68 ratio in mycosis fungoides and Sézary syndrome in correlation with serum sCD163 and CCL22

Abstract

Currently, there are no curative treatment options for mycosis fungoides (MF) and Sézary syndrome (SS) other than stem cell transplant. Understanding the interplay between tumor cells and tumor microenvironment could aid in the development of new therapies. Tumor-associated macrophages (TAMs) mostly have M2 phenotype that promotes tumor progression. This study investigated CD68+ and CD163+ TAMs as well as CD163/CD68 ratio in skin lesions from different stages of MF, large-plaque parapsoriasis, and SS. Moreover, we analyzed serum levels of sCD163 and CCL22 in correlation with TAMs count and CD163/CD68 ratio. CD68+ and CD163+ TAMs count significantly increased as the disease progressed. CD163/ CD68 ratio was highest at MF tumor stage and SS indicating M2 polarization with disease progression. Significant positive correlations were detected between serum levels of sCD163 and CCL22 and CD68+ and CD163+ TAMs count and CD163/ CD68 ratio. We concluded that TAMs play an important role in MF progression. High CD163/CD68 ratio in tumor stage MF and SS indicates M2 polarization of TAMs with tumor progression. CD163/CD68 ratio should be considered in assessing TAMs rather than total TAMs count. Also, sCD163 and CCL22 serum levels reflect M2 load and thus could be used as markers to assess disease progression.

Curcumin-Encapsulated Co-ZIF-8 for Ulcerative Colitis Therapy: ROS Scavenging and Macrophage Modulation Effects

“…CD68 and iNOS are proinflammatory cytokines, while CD163 and CD206 are anti-inflammatory cytokines that play important roles in controlling inflammation and immune response. , In order to explore the potential protective effect of CCM-Co-ZIF-8 against DSS-induced colitis in mice, the expression levels of CD68, iNOS, CD163, and CD206 were assessed. As shown in Figure a, in the CCM-Co-ZIF-8 treatment experiment, the expression levels of the CD68 and iNOS genes in the DSS group were increased by 0.52- and 1.4-folds, respectively, compared to the control group.…”

The Role of Tumor Microenvironment in the Pathogenesis of Sézary Syndrome

“…The release of IL-32 by NK cells, T-cells, keratinocytes, and fibroblasts may increase the M2 population in CTCL [80]. CD163/CD68 ratio was the highest at the MF tumor stage and Sézary syndrome, indicating M2 polarization with disease progression [81].…”

“…TAMs producing CCL18 are observed in CTCL patients, and serum levels of CCL18 are associated with a poorer prognosis [64,84]. Furthermore, increased CCL22 serum levels and sCD163 serum levels in CTCL reflect the increased activity of TAMs and tumor progression to a more advanced stage [81]. A strong correlation between macrophage depletion and decreased expression of a vascular marker, CD31, and lymphatic marker, podoplanin, suggest a role for macrophages in angiogenesis.…”