Osteosarcoma (OS) is the most common primary malignancy of the bone, highly aggressive and metastasizing, and it mainly affects children and adolescents. The current standard of care for OS is a combination of surgery and chemotherapy. However, these treatment options are not always successful, especially in cases of metastatic or recurrent osteosarcomas. For this reason, research into new therapeutic strategies is currently underway, and immunotherapies have received considerable attention. Mifamurtide stands out among the most studied immunostimulant drugs; nevertheless, there are very conflicting opinions on its therapeutic efficacy. Here, we aimed to investigate mifamurtide efficacy through in vitro and in vivo experiments. Our results led us to identify a new possible target useful to improve mifamurtide effectiveness on metastatic OS: the cytokine interleukin-10 (IL-10). We provide experimental evidence that the synergic use of an anti-IL-10 antibody in combination with mifamurtide causes a significantly increased mortality rate in highest-grade OS cells and lower metastasis in an in vivo model compared with mifamurtide alone. Overall, our data suggest that mifamurtide in combination with an anti-IL-10 antibody could be proposed as a new treatment protocol to be studied to improve the outcomes of OS patients.
骨肉瘤是最常见的原发性骨恶性肿瘤，具有高度侵袭性和转移性，主要影响儿童和青少年。目前骨肉瘤的标准治疗方案是手术联合化疗。然而，这些治疗方法并非总是成功，尤其是在转移性或复发性骨肉瘤病例中。因此，目前正在研究新的治疗策略，其中免疫疗法受到了广泛关注。在众多研究的免疫刺激药物中，米伐木肽备受关注；然而，关于其治疗效果存在很大争议。本研究旨在通过体外和体内实验探讨米伐木肽的疗效。我们的研究结果发现了一个可能提高米伐木肽对转移性骨肉瘤疗效的新靶点：细胞因子白细胞介素-10（IL-10）。我们提供的实验证据表明，与单独使用米伐木肽相比，在体内模型中联合使用抗IL-10抗体和米伐木肽能显著提高高级别骨肉瘤细胞的死亡率并减少转移。总体而言，我们的数据表明，米伐木肽联合抗IL-10抗体可能作为一种新的治疗方案进行研究，以改善骨肉瘤患者的预后。
Blockade of IL-10 Signaling Ensures Mifamurtide Efficacy in Metastatic Osteosarcoma
肿瘤(癌症)患者之家