Fig. 4
From: Cell therapy using ex vivo reprogrammed macrophages enhances antitumor immune responses in melanoma
Adoptive cell therapy of HDAC6 inhibitor treated M1 macrophages diminishes melanoma tumor growth in immunocompetent mice. (A) Schematic workflow of the macrophage adoptive cell therapy (ACT) in C57BL/6 syngeneic SM1 murine melanoma model. (n = 10 mice/group) (B) Tumor growth chart of SM1 melanoma tumors treated with vehicle (PBS), intratumor ACT of M1 (1 × 106) macrophages, injection of NextA (100ug), and intratumor ACT of M1 macrophages (1 × 106) pretreated with NextA (5µM) ex-vivo. (C) Survival analysis of mice treated with macrophage ACT. (D) Tumor growth chart of SM1 murine melanoma tumors with vehicle (PBS) or bone marrow-derived M1 macrophages from HDAC6KO mouse. (E) Flow cytometry-based immunophenotyping of M1, M2 macrophages as a fraction of F480 + Cd80 + and F4/80 + Cd206 + macrophages, respectively, and M1/M2 ratio in SM1 murine melanoma tumors treated with macrophage ACT. (F) CD8 T-cells as a fraction of Cd3 + cells. (G) CD4 T-cells, and T-regs as a fraction of Cd3 + cells. (H) Analysis of SM1 murine melanoma tumors treated with vehicle (Control), M1 macrophages, or HDAC6 inhibitor treated M1 macrophages (M1 + NextA) by hematoxylin and eosin (H&E) staining. Tumor stroma is indicated with white arrows. (I) Transplanted macrophages were derived from the bone marrow of UBC-GFP mice with ubiquitous GFP expression, enabling us to detect them by immunostaining with an anti-GFP antibody. (J-K) Immunohistochemistry staining to detect GFP-expressing macrophages, GFP and Cd38 expressing macrophages, GFP and Cd206 expressing M2 macrophages. White arrowheads indicate transplanted GFP macrophages. GFP expression is shown in black color. Cd38 and Cd206 expression are represented in brown color