巨噬细胞介导的细胞吞噬（MMCP）在抗肿瘤免疫疗法中起着关键作用，但通常被肿瘤细胞内在的吞噬逃避能力和免疫抑制性肿瘤微环境（TME）所限制。本研究通过封装粒细胞-巨噬细胞集落刺激因子（GM-CSF）和预先装载有涉胺霉素（Tuni）和过氧化氢酶（CAT）的治疗纳米平台（TCCaN），利用CaCO3纳米颗粒（NPs）的协助，精心设计了增强MMCP的水凝胶（TCCaGM）。值得注意的是，经过工程改造的水凝胶有效缓解了缺氧/酸性的TME，上调了“吞噬我”信号卡里内酰胺（CRT），同时下调了肿瘤细胞上的“不要吞噬我”信号CD47，还招募并激活了浸润的DCs，所有这些都有助于增强巨噬细胞介导的吞噬作用并引发肿瘤特异性CD8+ T细胞反应。与此同时，改造后的TME有利于加速肿瘤相关巨噬细胞（TAMs）向抗肿瘤的M1类型表型的极化，进一步增强抗肿瘤免疫力。通过与PD-1抗体（αPD-1）的联合作用，设计的水凝胶显著增强了全身性的抗肿瘤免疫反应，并具有长期的免疫效果，能够控制原发性和远处肿瘤的发展，并抑制肿瘤转移和复发，从而建立了高性能抗肿瘤免疫疗法的最佳策略。

Macrophage-mediated cellular phagocytosis (MMCP) plays a critical role in conducting antitumor immunotherapy but is usually impaired by the intrinsic phagocytosis evading ability of tumor cells and the immunosuppressive tumor microenvironment (TME). Herein, a MMCP-boosting hydrogel (TCCaGM) was elaborately engineered by encapsulating granulocyte-macrophage colony-stimulating factor (GM-CSF) and a therapeutic nanoplatform (TCCaN) that preloaded with the tunicamycin (Tuni) and catalase (CAT) with the assistance of CaCO3 nanoparticles (NPs). Strikingly, the hypoxic/acidic TME was efficiently alleviated by the engineered hydrogel, "eat me" signal calreticulin (CRT) was upregulated, while the "don't eat me" signal CD47 was downregulated on tumor cells, and the infiltrated DCs were recruited and activated, all of which contributed to boosting the macrophage-mediated phagocytosis and initiating tumor-specific CD8+ T cells responses. Meanwhile, the remodeled TME was beneficial to accelerate the polarization of tumor-associated macrophages (TAMs) to the antitumoral M1-like phenotype, further heightening tumoricidal immunity. With the combination of PD-1 antibody (αPD-1), the designed hydrogel significantly heightened systemic antitumor immune responses and long-term immunological effects to control the development of primary and distant tumors as well as suppress tumor metastasis and recurrence, which established an optimal strategy for high-performance antitumor immunotherapy.