Macrophage-derived chemokine CCL22 and regulatory T cells in ovarian cancer patients

Abstract

The study was undertaken to evaluate macrophage-derived chemokine (CCL22) levels in the peritoneal fluid (PF) and plasma of patients with ovarian cancer (n = 93) in relation to regulatory T cells (Tregs; n = 75). The peritoneal fluid CCL22 concentrations were significantly higher in epithelial ovarian cancer (EOC) patients than in patients with benign tumors-serous cystadenoma (n = 32). There was no difference in plasma levels of CCL22 in EOC patients compared with the non-cancer and healthy volunteers (n = 10). There were no significant differences in the plasma and PF CCL22 levels based on tumor grade. However, women with stage IV FIGO (International Federation of Gynecologists and Obstetricians) had significantly higher plasma CCL22 levels than patients with stages I and III. Women with stage I FIGO had significantly higher PF CCL22 levels than patients with stages II and III. Women with endometrioid cystadenocarcinoma had higher PF CCL22 levels than women with undifferentiated carcinoma. The percentage of tumor-infiltrating Tregs (11.06 %) was significantly higher compared to PF (3.05 %) and peripheral blood (PB) (2.01 %). Moreover, the percentage of Tregs was higher in the PF than in the PB of EOC patients. There were no significant differences in the PB, PF, and tumor-infiltrating Tregs percentage based on tumor stage, grade, or histology. Elevated levels of CCL22 found in the ascites could create a chemokine gradient aiding in Treg cells migration. Increased Tregs percentage in the local microenvironment of ovarian cancer might be an important mechanism of immunosuppression.

FAK inhibitors induce cell multinucleation and dramatically increase pro‐tumoral cytokine expression in RAW 264.7 macrophages

“…): IL‐1β (120.5 ± 9.7‐fold), IL‐1α (54.5 ± 10.1‐fold), IL‐6 (42.5 ± 3.4‐fold), CCL22 (59.2 ± 1.5‐fold), CCL17 (130.8 ± 1.5‐fold), and MMP12 (503.2 ± 2.5‐fold). Among them, CCL22, CCL17, IL‐6, and IL‐1β are well‐known pro‐tumoral cytokines that are able to stimulate tumor cell proliferation and invasion, as well as promote the suppression of antitumor immune responses . This study found that FAK inhibitor‐induced cell multinucleation resulted in a dramatic increase in several pro‐tumoral cytokines, suggesting the possibility of macrophages becoming pro‐tumoral.…”

Ccl22 Diverts T Regulatory Cells and Controls the Growth of Melanoma

“…As shown in Fig. 5A-C, in example FACS plots generated under each culture condition and 5D where Tregs are quantified, exposure to Ccl22 did not induce a greater Treg compartment among splenocytes at any tested concentration, even at higher than physiologic (serum) concentrations (21). However, comparing TGF-β treatment to untreated cells indicates a significant treatment effect by ANOVA ( P =0.0002), and the % of Treg is significantly different from untreated samples (P<0.05) at both 2 and 20 ng/mL using Dunnett's multiple comparison post-test.…”

Molecular Effects of Stromal-Selective Targeting by uPAR-Retargeted Oncolytic Virus in Breast Cancer

“…Other significantly down regulated genes that play a role in regulation of stromal cell components include FOS, EGR2, CREB-5, IL-6, Map2K1, among others (table S-1). At day 5, genes such as CCL22 [43], TIMD4 [44] and CCL19 [45], associated with macrophage networks were significantly down regulated.…”