尽管免疫疗法彻底改变了癌症治疗，但由于成熟树突状细胞（DC）浸润不足以及肿瘤微环境中免疫抑制细胞的高度扩散，免疫疗法在三阴性乳腺癌（TNBC）中的疗效受到严重限制。在此，我们设计了一种可以最大限度地激活树突状细胞的免疫调节纳米平台（HA/Lipo@MTO@IMQ），通过结合抑制性肿瘤免疫微环境逆转免疫疗法、化疗和光热疗法，显着根除肿瘤。人们注意到，这种三重辅助疗法可以显着提高免疫治疗效果：首先，盐酸米托蒽醌（MTO）诱导强大的免疫原性细胞死亡（ICD）效应，促进树突状细胞成熟和细胞毒性T淋巴细胞浸润。其次，Toll样受体7/8（TLR7/8）激动剂对DC的强大促成熟特性同时增强了ICD效应并限制了对瘤床和淋巴结的抗肿瘤免疫。在此基础上，肿瘤相关巨噬细胞响应 TLR7/8 激动剂，也显着向抗肿瘤 M1 表型重新极化，以增强吞噬作用并逆转免疫抑制微环境。此外，光热特性进一步促进了免疫活性细胞的募集和肿瘤生长抑制。该纳米平台没有明显的不良反应，表现出出色的激活全身免疫系统的能力，从而增加肿瘤微环境的免疫原性，从而增强肿瘤的杀伤作用。总而言之，HA/Lipo@MTO@IMQ 可能会凸显 TNBC 治疗方式的有效组合。

Despite immunotherapy having revolutionized cancer therapy, the efficacy of immunotherapy in triple-negative breast cancer (TNBC) is seriously restricted due to the insufficient infiltration of mature dendritic cells (DCs) and the highly diffusion of immunosuppressive cells in the tumor microenvironment. Herein, an immunomodulatory nanoplatform (HA/Lipo@MTO@IMQ), in which the DCs could be maximally activated, was engineered to remarkably eradicate the tumor via the combination of suppressive tumor immune microenvironment reversal immunotherapy, chemotherapy, and photothermal therapy. It was noticed that the immunotherapy efficacy could be significantly facilitated by this triple-assistance therapy: First, a robust immunogenic cell death (ICD) effect was induced by mitoxantrone hydrochloride (MTO) to boost DCs maturation and cytotoxic T lymphocytes infiltration. Second, the powerful promaturation property of the toll-like receptor 7/8 (TLR7/8) agonist on DCs simultaneously strengthened the ICD effect and restricted antitumor immunity to the tumor bed and lymph nodes. On this basis, tumor-associated macrophages were also dramatically repolarized toward the antitumor M1 phenotype in response to TLR7/8 agonist to intensify the phagocytosis and reverse the immunosuppressive microenvironment. Furthermore, the recruitment of immunocompetent cells and tumor growth inhibition were further promoted by the photothermal characteristic. The nanoplatform with no conspicuous untoward effects exhibited a splendid ability to activate the systemic immune system so as to increase the immunogenicity of the tumor microenvironment, thus enhancing the tumor killing effect. Taken together, HA/Lipo@MTO@IMQ might highlight an efficient combination of therapeutic modality for TNBC.