BACKGROUND: Tumor-associated M2 macrophages (TAMs) produce chemokines that affect the formation of cutaneous T-cell lymphoma (CTCL) by stromal factors. Since IFNs are an effective treatment for advanced-stage mycosis fungoides (MF), we hypothesized that IFNs might modulate M2 macrophages. OBJECTIVE: To prove our hypothesis, we stimulated monocyte-derived M2 macrophages with IFN-α2a or IFN-γ and examined the mRNA expression of chemokines. METHODS: By using a microarray, we selected a series of chemokines and MMPs that were strongly connected with the IL-4 stimulation. Then, we investigated the effects of IFN-α2a and IFN-γ on these chemokines. RESULTS: IFN-α2a and IFN-γ decreased the expression and production of CCL17 and CCL18 and increased those of CXCL10 and CXCL11. Moreover, the subcutaneous administration of IFN-α2a increased the CXCL11-producing cells in the lesional skin of patients with advanced MF. CONCLUSION: Our data suggest one possible mechanism of the therapeutic effects of IFNs through TAMs for the treatment of advanced-stage MF.
BACKGROUND: Tumor-associated M2 macrophages (TAMs) produce chemokines that affect the formation of cutaneous T-cell lymphoma (CTCL) by stromal factors. Since IFNs are an effective treatment for advanced-stage mycosis fungoides (MF), we hypothesized that IFNs might modulate M2 macrophages. OBJECTIVE: To prove our hypothesis, we stimulated monocyte-derived M2 macrophages with IFN-α2a or IFN-γ and examined the mRNA expression of chemokines. METHODS: By using a microarray, we selected a series of chemokines and MMPs that were strongly connected with the IL-4 stimulation. Then, we investigated the effects of IFN-α2a and IFN-γ on these chemokines. RESULTS: IFN-α2a and IFN-γ decreased the expression and production of CCL17 and CCL18 and increased those of CXCL10 and CXCL11. Moreover, the subcutaneous administration of IFN-α2a increased the CXCL11-producing cells in the lesional skin of patients with advanced MF. CONCLUSION: Our data suggest one possible mechanism of the therapeutic effects of IFNs through TAMs for the treatment of advanced-stage MF.
Authors: Bethany Mundy-Bosse; Nathan Denlinger; Eric McLaughlin; Nitin Chakravarti; Susan Hwang; Li Chen; Hsiaoyin Charlene Mao; David Kline; Youssef Youssef; Rebecca Kohnken; Dean Anthony Lee; Gerard Lozanski; Aharon G Freud; Pierluigi Porcu; Basem William; Michael A Caligiuri; Anjali Mishra Journal: Blood Adv Date: 2018-08-14
Authors: Thorbjørn Krejsgaard; Lise M Lindahl; Nigel P Mongan; Mariusz A Wasik; Ivan V Litvinov; Lars Iversen; Erik Langhoff; Anders Woetmann; Niels Odum Journal: Semin Immunopathol Date: 2016-10-07 Impact factor: 9.623