Department of Microbiology and Immunology, Medical School of Southeast University, Nanjing, China.
Front Immunol. 2021 Sep 13;12:707298. doi: 10.3389/fimmu.2021.707298. eCollection 2021.
We previously reported that enriched ubiquitinated proteins (UPs) from tumor cells have the potential to be used as immunotherapy vaccine against cancer. Here we enriched UPs from epirubicin (EPB)-induced multi-drug-resistant cancer stem-like breast cancer cell line (4T1/EPB) and tested the efficacy of α-AlO-UPs-4T1/EPB (short for UPs-4T1/EPB) as therapeutic vaccine alone and in combination with the stimulator of interferon genes (STING) agonist in mice with drug-resistant and metastatic breast cancer. Vaccination with UPs-4T1/EPB exerted profound anti-tumor effects through augmented specific CD8 T cell responses and amplified T cell receptor diversity of tumor-infiltrating lymphocytes (TILs). Importantly, the combination with STING agonist further facilitated the migration of mature CD8α dendritic cells to the lymph nodes and the infiltration of TILs within tumors, resulting in primary tumor regression and pulmonary metastasis eradication in mice. Moreover, the cured mice were completely resistant against a subsequent rechallenge with the same tumor. Our study indicates that this novel combinatorial immunotherapy with UPs-4T1/EPB vaccine and STING agonist is effective in mice with drug-resistant and metastatic breast cancer.
我们之前报道过，富含泛素化蛋白（UPs）的肿瘤细胞有可能被用作癌症免疫治疗疫苗。在这里，我们从表阿霉素（EPB）诱导的多药耐药性乳腺癌干细胞样细胞系（4T1/EPB）中富集 UPs，并测试了α-AlO-UPs-4T1/EPB（简称 UPs-4T1/EPB）作为治疗性疫苗单独使用以及与干扰素基因刺激物（STING）激动剂联合使用在具有耐药性和转移性乳腺癌的小鼠中的疗效。用 UPs-4T1/EPB 进行疫苗接种通过增强特异性 CD8 T 细胞反应和扩增肿瘤浸润淋巴细胞（TILs）的 T 细胞受体多样性发挥了深刻的抗肿瘤作用。重要的是，与 STING 激动剂联合使用进一步促进了成熟 CD8α树突状细胞向淋巴结的迁移以及 TILs 在肿瘤内的浸润，导致小鼠原发肿瘤消退和肺转移消除。此外，治愈的小鼠对随后用相同肿瘤进行的再挑战完全具有抗性。我们的研究表明，这种新型的联合免疫疗法，即 UPs-4T1/EPB 疫苗和 STING 激动剂联合使用，对具有耐药性和转移性乳腺癌的小鼠有效。
