Ivermectin converts cold tumors hot and synergizes with immune checkpoint blockade for treatment of breast cancer

摘要

4T1 breast tumors were isolated from mice that were untreated (left panels) or ivermectin-treated (right panels) daily for 14 days. Panels A, B show staining for HMGB1 (green), a hallmark of ICD. Panels C, D show staining for calreticulin (green), another hallmark of ICD. Staining for CK7 (red) identifies 4T1 cells. Data are representative of two independent experiments. Panels E, F show staining for CD4+ (green), CD8+ T cells (yellow), and cancer cells via staining for CK7 (red). Data are representative of three independent experiments. Panels G, H display quantitative data on T cell infiltration shown in E, F. Data were obtained by quantifying five random fields from whole tumor images. Panel I demonstrates the protective effect of prophylactic subcutaneous vaccination with 1 million 4T1 cells treated with 12 μM ivermectin ex vivo (24 h), then challenged contralaterally with live 4T1 cells 1 week post vaccination (n = 4). Statistical significance was evaluated using the linear mixed effects model of log tumor volume; *p ≤ 0.05, **p ≤ 0.01, ***p ≤ 0.001, ****p ≤ 0.0001.