Chen Yulin, Zhang Yi, Wang Jianjun, Cai Xiong, Chen Junzhang, Min Xiaobo, Xu Yunjie, Qin Qi, Wan Chidan
Department of Hepatobiliary Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People's Republic of China.
Hubei Engineering Research Center of Tumor-Targeted Biochemotherapy, Wuhan, 430030, People's Republic of China.
Int J Nanomedicine. 2024 Mar 6;19:2227-2239. doi: 10.2147/IJN.S449694. eCollection 2024.
Hepatocellular Carcinoma (HCC) poses significant challenges due to limited effective treatments and high recurrence rates. Immunotherapy, a promising approach, faces obstacles in HCC patients due to T-cell exhaustion and immunosuppression within the tumor microenvironment.
Using doxorubicin-loaded tumor-derived microparticles (Dox-TMPs), the mice with H22 ascites model and subcutaneous tumors model were treated. Following the treatment, mice were re-challenged with H22 cells to compare the therapeutic effects and recurrence among different groups of mice, alongside examining the changes in the proportions of immune cells within the tumor microenvironment. Furthermore, Dox-TMPs were combined with anti-PD-1 to further validate their anti-tumor efficacy. In vitro studies using various liver cancer cell lines were conducted to verify the tumor-killing effects of Dox-TMPs. Additionally, CD8+ T cells from the abdominal cavity of tumor-free mice were co-cultured with H22 cells to confirm their specific tumor-killing abilities.
Dox-TMPs demonstrate effective anti-tumor effects both in vitro and in vivo. In vivo, their effectiveness primarily involves enhancing CD8+ T cell infiltration, alleviating T cell immunosuppression, and improving the immune microenvironment to combat tumors. When used in combination with anti-PD-1, their anti-tumor effects are further enhanced. Moreover, some mice treated with Dox-TMPs developed anti-tumor immunity, displaying a self-specific T-cell immune response upon re-challenged with tumor cells. This suggests that Dox-TMPs also have the potential to act as a long-term immune response against tumor recurrence, indicating their capability as a tumor vaccine.
Dox-TMPs exhibit a dual role in liver cancer by regulating T cells within the tumor microenvironment, functioning both as an anti-tumor agent and a potential tumor vaccine.
由于有效治疗方法有限且复发率高，肝细胞癌（HCC）带来了重大挑战。免疫疗法是一种有前景的方法，但由于肿瘤微环境中的T细胞耗竭和免疫抑制，在HCC患者中面临障碍。
使用载有阿霉素的肿瘤衍生微粒（Dox-TMPs）对H22腹水模型和皮下肿瘤模型小鼠进行治疗。治疗后，用H22细胞对小鼠进行再次攻击，以比较不同组小鼠的治疗效果和复发情况，同时检查肿瘤微环境中免疫细胞比例的变化。此外，将Dox-TMPs与抗PD-1联合使用，以进一步验证其抗肿瘤疗效。进行了使用各种肝癌细胞系的体外研究，以验证Dox-TMPs的肿瘤杀伤作用。此外，将无肿瘤小鼠腹腔中的CD8+T细胞与H22细胞共培养，以确认其特异性肿瘤杀伤能力。
Dox-TMPs在体外和体内均表现出有效的抗肿瘤作用。在体内，其有效性主要涉及增强CD8+T细胞浸润、减轻T细胞免疫抑制以及改善免疫微环境以对抗肿瘤。与抗PD-1联合使用时，其抗肿瘤作用进一步增强。此外，一些接受Dox-TMPs治疗的小鼠产生了抗肿瘤免疫力，在再次受到肿瘤细胞攻击时表现出自身特异性T细胞免疫反应。这表明Dox-TMPs也有可能作为针对肿瘤复发的长期免疫反应，表明其作为肿瘤疫苗的能力。
Dox-TMPs通过调节肿瘤微环境中的T细胞在肝癌中发挥双重作用，既作为抗肿瘤剂又作为潜在的肿瘤疫苗。
