Aiiso Yufeng Li Family Department of Chemical and Nano Engineering, University of California, San Diego, 9500 Gilman Dr., La Jolla, CA, 92093, USA.
Aiiso Yufeng Li Family Department of Chemical and Nano Engineering, University of California, San Diego, 9500 Gilman Dr., La Jolla, CA, 92093, USA; Center for Nano-ImmunoEngineering, University of California, San Diego, 9500 Gilman Dr., La Jolla, CA, 92093, USA; Moores Cancer Center, University of California, San Diego, 9500 Gilman Dr., La Jolla, CA, 92093, USA.
Biomaterials. 2024 Dec;311:122663. doi: 10.1016/j.biomaterials.2024.122663. Epub 2024 Jun 10.
Ovarian cancer (OvCa) is a leading cause of mortality among gynecological malignancies and usually manifests as intraperitoneal spheroids that generate metastases, ascites, and an immunosuppressive tumor microenvironment. In this study, we explore the immunomodulatory properties of cowpea mosaic virus (CPMV) as an adjuvant immunotherapeutic agent using an in vitro model of OvCa peritoneal spheroids. Previous findings highlighted the potent efficacy of intratumoral CPMV against OvCa in mouse tumor models. Leveraging the precision control over material deposition and cell patterning afforded by digital-light-processing (DLP) based bioprinting, we constructed OvCa-macrophage spheroids to mimic peritoneal spheroids using gelatin methacrylate (GelMA), a collagen-derived photopolymerizable biomaterial to mimic the extracellular matrix. Following CPMV treatment, bioprinted spheroids exhibited inhibited OvCa progression mediated by macrophage activation. Our analysis indicates that CPMV regulates and activates macrophage to both induce OvCa cell killing and restore normal cell-cell junctions. This study deepened our understanding of the mechanism of CPMV intratumoral immunotherapy in the setting of OvCa. This study also highlights the potential of studying immunotherapies using high throughput tissue models via DLP bioprinting.
卵巢癌（OvCa）是妇科恶性肿瘤死亡的主要原因，通常表现为产生转移、腹水和免疫抑制肿瘤微环境的腹腔球体。在这项研究中，我们使用 OvCa 腹腔球体的体外模型探索豇豆花叶病毒（CPMV）作为佐剂免疫治疗剂的免疫调节特性。先前的研究结果强调了肿瘤内 CPMV 对小鼠肿瘤模型中 OvCa 的强大疗效。利用数字光处理（DLP）基生物打印提供的对材料沉积和细胞图案化的精确控制，我们使用明胶甲基丙烯酰胺（GelMA）构建 OvCa-巨噬细胞球体，以模拟胶原衍生的光聚合生物材料的细胞外基质。在 CPMV 处理后，生物打印的球体表现出由巨噬细胞激活介导的抑制 OvCa 进展。我们的分析表明，CPMV 调节和激活巨噬细胞，以诱导 OvCa 细胞杀伤并恢复正常细胞-细胞连接。这项研究加深了我们对 OvCa 中 CPMV 肿瘤内免疫治疗机制的理解。这项研究还强调了通过 DLP 生物打印使用高通量组织模型研究免疫疗法的潜力。
