CD206‐positive myeloid cells bind galectin‐9 and promote a tumor‐supportive microenvironment

Abstract

In patients with metastatic melanoma, high blood levels of galectin-9 are correlated with worse overall survival and a bias towards a Th2 inflammatory state supportive of tumor growth. Although galectin-9 signaling through TIM3 on T cells has been described, less is known about the interaction of galectin-9 with macrophages. We aimed to determine whether galectin-9 is a binding partner of CD206 on macrophages and whether the result of this interaction is tumor-supportive. It was determined that incubation of CD68 macrophages with galectin-9 or anti-CD206 blocked target binding and that both CD206 and galectin-9 were detected by immunoprecipitation of cell lysates. CD206 and galectin-9 had a binding affinity of 2.8 × 10 m. Galectin-9 causes CD206 macrophages to make significantly more FGF2 and monocyte chemoattractant protein (MCP-1), but less macrophage-derived chemokine (MDC). Galectin-9 had no effect on classical monocyte subsets, but caused expansion of the non-classical populations. Lastly, there was a positive correlation between increasing numbers of CD206 macrophages and galectin-9 expression in tumors, and high levels of CD206 macrophages correlated negatively with melanoma survival. These results indicate that galectin-9 binds to CD206 on M2 macrophages, which appear to drive angiogenesis and the production of chemokines that support tumor growth and poor patient prognoses. Targeting this interaction systemically through circulating monocytes may therefore be a novel way to improve local anti-tumor effects by macrophages. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Loss of Osteopontin Expression Reduces HSV-1-Induced Corneal Opacity

“…tion in FGF-2 expression, consistent with our previous findings suggesting that FGF-2 is a critical factor during this time period. 10 Because macrophages are a source of FGF-2 and can cleave matrix-bound FGF-2 produced by corneal epithelial cells, fibroblasts, and endothelial cells, [47][48][49] the depletion of macrophages is consistent with the outcome observed in the current dataset. The peak of CD64 + CD206 + macrophages occurred at day 14 pi with the FGF-2 levels recovered in the infected cornea, as these cells are a source of FGF-2.…”

“…The peak of CD64 + CD206 + macrophages occurred at day 14 pi with the FGF-2 levels recovered in the infected cornea, as these cells are a source of FGF-2. 48 However, we cannot discount the potential contribution of the unique neutrophil (CD45 + CD11b + Ly6G + Ly6C mid CCR2 +/-GFP + ) population to the NV process. The CD64 + CD206 + macrophages were also CCR2 + , thought to be recruited from circulation during inflammation.…”

In-depth plasma proteomics reveals increase in circulating PD-1 during anti-PD-1 immunotherapy in patients with metastatic cutaneous melanoma

“…11 21 Altogether, some of these findings coincide with previous reports on the involvement of immunological proteins in antitumor response to CM. [22][23][24][25][26][27][28] Protein plasma levels can predict PFs To detect potential predictive biomarkers, we also analyzed the association between pre-trm plasma protein levels and PFS. No clinical variables were associated with PFS in the HiRIEF LC-MS/MS-analyzed subgroup of anti-PD-1 treatment cohort (n=13); therefore we performed univariate analyses, which showed associations between protein pre-trm plasma levels of 109 proteins and PFS in this cohort (p<0.05, no FDR; online supplementary table S8, additional file 2).…”

Research Progress on Tumor-Associated Macrophages and Inflammation in Cervical Cancer

“…e M2 antigen presentation ability is weakened, the antitumor activity is low, and the ability to support angiogenesis and tissue remodeling is enhanced, which is beneficial to tumor growth and invasion [28,29]. High levels of FGF-2, MCP-1, CXCL12, and VEGF in TME were associated with an increase in the number of M2 cells [26,30]. It will be a new research direction in the future to develop a new therapy for tumors by targeting TAMs [31].…”