Efferocytosis inhibition is emerging as an attractive strategy for antitumor immune therapy because of the subsequent leak of abundant immunogenic contents. However, the practical efficacy is seriously impeded by the immunosuppressive tumor microenvironments. Here, we construct a versatile nanosystem that can not only inhibit the efferocytosis but also boost the following antitumor immunity. MerTK inhibitor UNC2025 is loaded into the bacterial outer membrane vesicles (OMVs), which are then modified with maleimide (mU@OMVs). The prepared mU@OMVs effectively inhibits the efferocytosis by promoting the uptake while preventing the MerTK phosphorylation of tumor associated macrophages, and then captures the released antigens through forming universal thioether bonds. The obtained in situ vaccine effectively transfers to lymph nodes by virtue of the intrinsic features of OMVs, and then provokes intense immune responses that can efficiently prevent the growth, metastasis and recurrence of tumors in mice, providing a generalizable strategy for cancer immunotherapy.

细胞增多症抑制正在成为抗肿瘤免疫治疗的一种有吸引力的策略，因为随后会泄漏大量的免疫原性内容物。然而，免疫抑制性肿瘤微环境严重阻碍了实际疗效。在这里，我们构建了一个多功能的纳米系统，它不仅可以抑制胞吐作用，还可以增强后续的抗肿瘤免疫力。MerTK 抑制剂 UNC2025 被加载到细菌外膜囊泡 (OMV) 中，然后用马来酰亚胺 (mU@OMV) 对其进行修饰。制备的 mU@OMVs 通过促进摄取有效抑制胞吐作用，同时防止肿瘤相关巨噬细胞的 MerTK 磷酸化，然后通过形成通用硫醚键捕获释放的抗原。