Efficacy of IFN-γ, sCD40L, and Poly(I:C) Treated Bone Marrow-Derived Macrophages in Murine Mammary Carcinoma

• Published in: Immunological investigations 2024-08, Vol.53 (6), p.857-871
• Main Authors: Roberts, Meghan, Finn, Joshua, Lass, Melissa, Oviedo-Bermudez, Ernesto, Kurt, Robert A
• Format: Article
• Language: English
• Subjects: Animals; B7-1 Antigen - metabolism; CD40 Ligand - metabolism; Cell Line, Tumor; Cytokines - metabolism; Female; Histocompatibility Antigens Class II - genetics; Histocompatibility Antigens Class II - metabolism; Interferon-gamma - metabolism; Macrophages - drug effects; Macrophages - immunology; Macrophages - metabolism; Mammary Neoplasms, Experimental - drug therapy; Mammary Neoplasms, Experimental - immunology; Mammary Neoplasms, Experimental - pathology; Mice; Mice, Inbred BALB C; Poly I-C - pharmacology
• ISSN: 0882-0139; 1532-4311; 1532-4311
• DOI: 10.1080/08820139.2024.2354264

Here, we explored methods to generate anti-tumor bone marrow-derived macrophages (BMDM) and how delivery of the BMDM at early tumor sites could impact disease progression. BMDM treated with IFN-γ, sCD40L, poly(I:C), and a combination of the three were assessed. Treatment with sCD40L had no significant impact on the BMDM. Treating BMDM with IFN-γ impacted IL-1β, MHC Class II, and CD80 expression. While poly(I:C) treatment had a greater impact on the BMDM than IFN-γ when assessed by the  assays, the BMDM treated with poly (I:C) had mixed results   where they decreased growth of the EMT6 tumor, did not impact growth of the 168 tumor, and enhanced growth of the 4T1 tumor. The combination of poly(I:C), IFN-γ, and sCD40L had the greatest impact on the BMDM  and  . Treatment with all three agonists resulted in increased IL-1β, TNF-α, and IL-12 expression, decreased expression of arginase and mrc, increased phagocytic activity, nitrite production, and MHC Class II and CD80 expression, and significantly impacted growth of the EMT6 and 168 murine mammary carcinoma models. Collectively, these data show that treating BMDM with poly(I:C), IFN-γ, and sCD40L generates BMDM with more consistent anti-tumor activity than BMDM generated with the individual agonists.