Tumor-associated macrophages (TAMs) promote metastasis and inhibit T cells, but macrophages can be polarized to kill cancer cells. Macrophage polarization could thus be a strategy for controlling cancer. We show that macrophages from metastatic pleural effusions of breast cancer patients can be polarized to kill cancer cells with monophosphoryl lipid A (MPLA) and interferon (IFN) γ. MPLA + IFNγ injected intratumorally or intraperitoneally reduces primary tumor growth and metastasis in breast cancer mouse models, suppresses metastasis, and enhances chemotherapy response in an ovarian cancer model. Both macrophages and T cells are critical for the treatment's anti-metastatic effects. MPLA + IFNγ stimulates type I IFN signaling, reprograms CD206⁺ TAMs to inducible NO synthase (iNOS)⁺ macrophages, and activates cytotoxic T cells through macrophage-secreted interleukin-12 (IL-12) and tumor necrosis factor alpha (TNFα). MPLA and IFNγ are used individually in clinical practice and together represent a previously unexplored approach for engaging a systemic anti-tumor immune response.

肿瘤相关巨噬细胞 (TAM) 促进转移并抑制 T 细胞，但巨噬细胞可以极化以杀死癌细胞。因此，巨噬细胞极化可能是控制癌症的一种策略。我们表明，来自乳腺癌患者转移性胸腔积液的巨噬细胞可以极化，以用单磷酰脂质 A (MPLA) 和干扰素 (IFN) γ 杀死癌细胞。瘤内或腹膜内注射 MPLA + IFNγ 可减少乳腺癌小鼠模型中的原发性肿瘤生长和转移，抑制转移，并增强卵巢癌模型中的化疗反应。巨噬细胞和 T 细胞对于治疗的抗转移作用都至关重要。MPLA + IFNγ 刺激 I 型 IFN 信号传导，将 CD206 ⁺ TAM 重编程为诱导型 NO 合酶 (iNOS) ⁺巨噬细胞，并通过巨噬细胞分泌的白细胞介素 12 (IL-12) 和肿瘤坏死因子 α (TNFα) 激活细胞毒性 T 细胞。MPLA 和 IFNγ 在临床实践中单独使用，它们共同代表了一种以前未开发的用于参与系统性抗肿瘤免疫反应的方法。