肿瘤原位疫苗接种（ISV）策略已在临床试验中成为有前途的方法，包括通过局部放疗和瘤内辅助注射释放肿瘤抗原。然而，目前实现 ISV 可持续免疫反应的制造策略仍然是一个紧迫的挑战。在这项研究中，我们提出了一种使用 177Lu 标记的锰掺杂介孔羟基磷灰石 (177Lu/Mn-HAP) 微球进行抗肿瘤治疗的可持续 ISV 方法。 ISV 能够持续利用肿瘤抗原，导致树突状细胞激活和巨噬细胞向 M1 亚型极化。因此，它有助于产生有效的 CD8 T 细胞反应，增强内放射对原发肿瘤和远处肿瘤的抗肿瘤作用。重要的是，这种方法使所有荷瘤小鼠获得完全缓解，并刺激免疫记忆以防止肿瘤复发。我们的研究强调了一种通用且安全的 ISV 策略，能够诱导有效的肿瘤特异性和可持续的免疫反应。

Tumor in situ vaccination (ISV) strategies have emerged in clinical trials as promising approaches, involving the release of tumor antigens through local radiotherapy and intratumorally adjuvant injections. However, the current fabrication strategy for achieving a sustainable immune response to ISV remains a pressing challenge. In this study, we present an empowered sustainable ISV method for antitumor therapy using 177Lu-labeled manganese-doped mesoporous hydroxyapatite (177Lu/Mn-HAP) microspheres. The ISV enables the sustained utilization of tumor antigens, leading to the activation of dendritic cells and polarization of macrophages toward the M1 subtype. Consequently, it facilitates the generation of potent CD8+ T-cell responses, enhancing the antitumor effects of internal radiation in both primary and distant tumors. Importantly, this approach achieves complete remission in all tumor-bearing mice and stimulates immune memory to prevent tumor recurrence. Our study highlights a universal and safe ISV strategy capable of inducing potent tumor-specific and sustainable immune response.