中文摘要：
免疫疗法是治疗转移性乳腺癌（MBC）的一种前景广阔的策略，为临床治疗提供了新的可能性。尽管免疫检查点抑制剂在转移性乳腺癌的治疗中已取得显著进展，但其在骨转移患者中的疗效却令人失望。这种疗效不佳似乎与骨微环境的免疫抑制特征密切相关。在本研究中，我们阐明了唾液酸结合免疫球蛋白样凝集素-15（Siglec-15）/唾液酸糖免疫检查点轴在骨转移微环境中的多重作用，并探索了靶向该糖免疫检查点的潜在治疗策略。我们的研究揭示，骨转移微环境中Siglec-15水平升高可促进肿瘤诱导的破骨细胞生成，同时抑制抗原特异性T细胞反应。进一步研究表明，采用抗体阻断Siglec-15/唾液酸糖免疫检查点轴，可作为乳腺癌骨转移的潜在治疗手段。通过靶向这一通路，我们不仅旨在治疗骨转移，还试图抑制转移性癌细胞从骨病灶向其他器官的播散。
英文摘要：
Immunotherapy is a promising approach for treating metastatic breast cancer (MBC), offering new possibilities for therapy. While checkpoint inhibitors have shown great progress in the treatment of metastatic breast cancer, their effectiveness in patients with bone metastases has been disappointing. This lack of efficacy seems to be specific to the bone environment, which exhibits immunosuppressive features. In this study, we elucidate the multiple roles of the sialic acid–binding Ig-like lectin (Siglec)-15/sialic acid glyco-immune checkpoint axis in the bone metastatic niche and explore potential therapeutic strategies targeting this glyco-immune checkpoint. Our research reveals that elevated levels of Siglec-15 in the bone metastatic niche can promote tumor-induced osteoclastogenesis as well as suppress antigen-specific T cell responses. Next, we demonstrate that antibody blockade of the Siglec-15/sialic acid glyco-immune checkpoint axis can act as a potential treatment for breast cancer bone metastasis. By targeting this pathway, we not only aim to treat bone metastasis but also inhibit the spread of metastatic cancer cells from bone lesions to other organs.
论文信息：
论文题目：Siglec-15/sialic acid axis as a central glyco-immune checkpoint in breast cancer bone metastasis
期刊名称：PNAS
时间期卷：121 (5) e2312929121
在线时间：2024年1月22日
DOI: 10.1073/pnas.231292912
产品信息：
货号：C-010
规格：10ml
品牌：Liposoma
产地：荷兰
名称：Clodronate Liposomes
办事处：靶点科技
Clodronate Liposomes氯膦酸盐脂质体清除乳腺癌骨转移模型里巨噬细胞。荷兰Liposoma巨噬细胞清除剂ClodronateLiposomes见刊于PNAS：Siglec-15/唾液酸轴是乳腺癌骨转移中一个核心的糖免疫检查点。
Liposoma巨噬细胞清除剂Clodronate Liposomes氯膦酸二钠脂质体清除巨噬细胞的材料和方法：
In vivo macrophage depletion
For osteoclast (macrophages) depletion study, clodronate liposome (C-010, Liposoma BV) was injected intraperitoneally at 4-d intervals from 6 d before tumor inoculation and repeated for four times at a dose of 0.3 mL of liposomes as reported previously (52–54).
巨噬细胞清除材料和方法文献截图：
