中文摘要：

免疫療法是治療轉移性乳腺癌（MBC）的一種前景廣闊的策略，為臨床治療提供了新的可能性。盡管免疫檢查點抑制劑在轉移性乳腺癌的治療中已取得顯著進展，但其在骨轉移患者中的療效卻令人失望。這種療效不佳似乎與骨微環境的免疫抑制特征密切相關。在本研究中，我們闡明了唾液酸結合免疫球蛋白樣凝集素-15（Siglec-15）/唾液酸糖免疫檢查點軸在骨轉移微環境中的多重作用，并探索了靶向該糖免疫檢查點的潛在治療策略。我們的研究揭示，骨轉移微環境中Siglec-15水平升高可促進腫瘤誘導的破骨細胞生成，同時抑制抗原特異性T細胞反應。進一步研究表明，采用抗體阻斷Siglec-15/唾液酸糖免疫檢查點軸，可作為乳腺癌骨轉移的潛在治療手段。通過靶向這一通路，我們不僅旨在治療骨轉移，還試圖抑制轉移性癌細胞從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.

論文信息：

論文題目：Siglec-15/sialic acid axis as a central glyco-immune checkpoint in breast cancer bone metastasis

期刊名稱：PNAS

時間期卷：121 (5) e2312929121

在線時間：2024年1月22日

DOI: 10.1073/pnas.231292912

產品信息：

貨號：C-010

規格：10ml

品牌：Liposoma

產地：荷蘭

名稱：Clodronate Liposomes

辦事處：靶點科技

Clodronate Liposomes氯膦酸鹽脂質體清除乳腺癌骨轉移模型里巨噬細胞。荷蘭Liposoma巨噬細胞清除劑ClodronateLiposomes見刊于PNAS：Siglec-15/唾液酸軸是乳腺癌骨轉移中一個核心的糖免疫檢查點。

Liposoma巨噬細胞清除劑Clodronate Liposomes氯膦酸二鈉脂質體清除巨噬細胞的材料和方法：

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).

巨噬細胞清除材料和方法文獻截圖：