Osteosarcoma (OsA) has limited treatment options and stagnant 5-year survival rates. Its immune microenvironment is characterized by a predominance of tumor-associated macrophages (TAMs), whose role in OsA progression remain unclear. Nevertheless, immunotherapies aiming to modulate macrophages activation and polarization could be of interest for OsA treatment. In this study, the antitumor effect of a liposome-encapsulated chemically detoxified lipopolysaccharide (Lipo-MP-LPS) was evaluated as a therapeutic approach for OsA. Lipo-MP-LPS is a toll-like receptor 4 (TLR4) agonist sufficiently safe and soluble to be IV administered at effective doses. Lipo-MP-LPS exhibited a significant antitumor response, with tumor regression in 50% of treated animals and delayed tumor progression in the remaining 50%. The agent inhibited tumor growth by 75%, surpassing the efficacy of other immunotherapies tested in OsA. Lipo-MP-LPS modulated OsA’s immune microenvironment by favoring the transition of M2 macrophages to M1 phenotype, creating a proinflammatory milieu and facilitating T-cell recruitment and antitumor immune response. Overall, the study demonstrates the potent antitumor effect of Lipo-MP-LPS as monotherapy in an OsA immunocompetent model. Reprogramming macrophages and altering the immune microenvironment likely contribute to the observed tumor control. These findings support the concept of immunomodulatory approaches for the treatment of highly resistant tumors like OsA.
骨肉瘤的治疗选择有限，五年生存率长期停滞不前。其免疫微环境以肿瘤相关巨噬细胞占主导地位为特征，而该细胞在骨肉瘤进展中的作用尚不明确。尽管如此，旨在调控巨噬细胞活化与极化的免疫疗法可能为骨肉瘤治疗提供新思路。本研究评估了脂质体包裹化学脱毒脂多糖（Lipo-MP-LPS）作为骨肉瘤治疗手段的抗肿瘤效应。Lipo-MP-LPS作为一种Toll样受体4激动剂，具有足够的安全性和溶解性，可通过静脉注射达到有效治疗剂量。实验显示Lipo-MP-LPS能显著抑制肿瘤生长：50%的受试动物出现肿瘤消退，其余50%肿瘤进展延迟。该制剂使肿瘤生长抑制率达75%，其疗效优于其他已测试的骨肉瘤免疫疗法。Lipo-MP-LPS通过促进M2型巨噬细胞向M1型转化，重塑骨肉瘤免疫微环境，形成促炎性环境并促进T细胞募集，从而激发抗肿瘤免疫应答。本研究证实，在免疫健全的骨肉瘤模型中，Lipo-MP-LPS单药治疗具有强大的抗肿瘤效果。巨噬细胞重编程与免疫微环境改变可能是实现肿瘤控制的关键机制。这些发现为采用免疫调节疗法治疗骨肉瘤等高耐药性肿瘤提供了理论依据。
肿瘤(癌症)患者之家