Hung Yi-Ping, Tu Chia-Chun, Lai Jiun-I, Yang Muh-Hwa, Lee Jan-Mou, Chao Yee
Division of Medical Oncology, Department of Oncology, Taipei Veterans General Hospital, Taipei, Taiwan.
Institute of Clinical Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.
BMC Cancer. 2024 Jan 26;24(1):136. doi: 10.1186/s12885-024-11889-4.
Despite the utilization of immune checkpoint inhibitors (ICIs) in treating numerous types of cancers being approved, their efficacy in tumor control in the clinic is not satisfactory. Since adoptive cell therapy (ACT) can alter the tumor microenvironment, we hypothesized that ACT potentially synergized with ICI in tumor control and examined this hypothesis via a murine allograft model.
Female C57BL/6 mice were stimulated with interleukin 15 and granulocyte monocyte-colony stimulating factor, followed by collecting their bone marrow cells for murine NKDC cultivation. Then, female C57BL/6 mice, inoculated with lymphoma cancer cell line E.G7-OVA, were administrated with murine NKDC cells, murine anti-program cell death ligand-1 antibody (α-mPD-L1), or both for 28 days. After 28 days of treatment, mice were sacrificed whose inoculated tumors, spleen, sentinel lymph nodes, and peripheral blood were collected to measure tumor size, lymphocyte infiltration, and change of immune cell profile.
Combined treatment of NKDCs with α-mPD-L1 exhibited significantly stronger tumor control efficacy than treatment of NKDCs or α-mPD-L1 alone. NKDCs/α-mPD-L1 combination increased migration of dendritic cells, CD4, CD8 T cells, and activated CD8 T cells to the tumor-bedding site, and promoted endogenous tumor-specific cytotoxic T-cell response.
The current study confirmed our hypothesis that combining NKDC ACT with ICI therapy can potentiate tumor control efficacy by manipulating the tumor microenvironment. This study provided a novel circumstance on tumor immunotherapy.
尽管免疫检查点抑制剂（ICI）在多种癌症治疗中的应用已获批准，但其在临床肿瘤控制中的疗效并不令人满意。由于过继性细胞疗法（ACT）可改变肿瘤微环境，我们推测ACT可能与ICI在肿瘤控制方面具有协同作用，并通过小鼠同种异体移植模型对这一假设进行了验证。
用白细胞介素15和粒细胞-单核细胞集落刺激因子刺激雌性C57BL/6小鼠，随后收集其骨髓细胞用于培养小鼠自然杀伤树突状细胞（NKDC）。然后，给接种淋巴瘤癌细胞系E.G7-OVA的雌性C57BL/6小鼠注射小鼠NKDC细胞、小鼠抗程序性细胞死亡配体1抗体（α-mPD-L1）或两者，持续28天。治疗28天后，处死小鼠，收集接种的肿瘤、脾脏、前哨淋巴结和外周血，以测量肿瘤大小、淋巴细胞浸润和免疫细胞谱的变化。
NKDC与α-mPD-L1联合治疗显示出比单独使用NKDC或α-mPD-L1治疗更强的肿瘤控制疗效。NKDC/α-mPD-L1联合治疗增加了树突状细胞、CD4、CD8 T细胞和活化CD8 T细胞向肿瘤床部位的迁移，并促进了内源性肿瘤特异性细胞毒性T细胞反应。
本研究证实了我们的假设，即NKDC ACT与ICI疗法联合应用可通过调控肿瘤微环境增强肿瘤控制疗效。本研究为肿瘤免疫治疗提供了新的情况。
