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

ABSTRACT

Introduction

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.

Methods

BMDM treated with IFN-γ, sCD40L, poly(I:C), and a combination of the three were assessed.

Results

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 in vitro assays, the BMDM treated with poly (I:C) had mixed results in vivo 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 in vitro and in vivo. 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.

Discussion

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.

KEYWORDS:

• Bone marrow-derived macrophages
• IFN-gamma
• murine mammary carcinoma
• poly(I:C)
• soluble CD40L

Acknowledgments

The Excel Scholar Program and The Department of Biology at Lafayette College supported this work.

Disclosure statement

No potential conflict of interest was reported by the author(s).