Sorafenib plus memory-like natural killer cell immunochemotherapy boosts treatment response in liver cancer

作者：Aydın Eresen, Zigeng Zhang, Zigeng Zhang, Guangbo Yu, Qiaoming Hou, Zhilin Chen, Zeyang Yu, Vahid Yaghmai, Zhuoli Zhang, Zhuoli Zhang · 发表于：BMC Cancer · 年份：2024 · DOI：10.1186/s12885-024-12718-4 · 被引用次数：4 · 研究领域：Immune Cell Function and Interaction、Cancer Immunotherapy and Biomarkers、Hepatocellular Carcinoma Treatment and Prognosis

BACKGROUND: Heterogeneity of hepatocellular carcinoma (HCC) presents significant challenges for therapeutic strategies and necessitates combinatorial treatment approaches to counteract suppressive behavior of tumor microenvironment and achieve improved outcomes. Here, we employed cytokines to induce memory-like behavior in natural killer (NK) cells, thereby enhancing their cytotoxicity against HCC. Additionally, we evaluated the potential benefits of combining sorafenib with this newly developed memory-like NK cell (pNK) immunochemotherapy in a preclinical model. METHODS: HCC tumors were grown in SD rats using subcapsular implantation. Interleukin 12/18 cytokines were supplemented to NK cells to enhance cytotoxicity through memory activation. Tumors were diagnosed using MRI, and animals were randomly assigned to control, pNK immunotherapy, sorafenib chemotherapy, or combination therapy groups. NK cells were delivered locally via the gastrointestinal tract, while sorafenib was administered systemically. Therapeutic responses were monitored with weekly multi-parametric MRI scans over three weeks. Afterward, tumor tissues were harvested for histopathological analysis. Structural and functional changes in tumors were evaluated by analyzing MRI and histopathology data using ANOVA and pairwise T-test analyses. RESULTS: The tumors were allowed to grow for six days post-cell implantation before treatment commenced. At baseline, tumor diameter averaged 5.27 mm without significant diff...