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Immunological conversion of solid tumours using a bispecific nanobioconjugate for cancer immunotherapy
Nature Nanotechnology ( IF 38.1 ) Pub Date : 2022-11-10 , DOI: 10.1038/s41565-022-01245-7
Yifei Lu 1, 2 , Kristin Huntoon 1, 2 , DaeYong Lee 1, 2 , Yifan Wang 3 , JongHoon Ha 3 , Yaqing Qie 1, 2 , Xuefeng Li 3 , Benjamin R Schrank 3 , Shiyan Dong 3 , Thomas D Gallup 1 , Minjeong Kang 3 , Hai Zhao 1, 2 , Yi An 4 , Zhaogang Yang 3 , Jing Li 3 , Betty Y S Kim 1, 2 , Wen Jiang 3
Affiliation  

Solid tumours display a limited response to immunotherapies. By contrast, haematological malignancies exhibit significantly higher response rates to immunotherapies as compared with solid tumours. Among several microenvironmental and biological disparities, the differential expression of unique immune regulatory molecules contributes significantly to the interaction of blood cancer cells with immune cells. The self-ligand receptor of the signalling lymphocytic activation molecule family member 7 (SLAMF7), a molecule that is critical in promoting the body’s innate immune cells to detect and engulf cancer cells, is expressed nearly exclusively on the cell surface of haematologic tumours, but not on solid ones. Here we show that a bispecific nanobioconjugate that enables the decoration of SLAMF7 on the surface of solid tumours induces robust phagocytosis and activates the phagocyte cyclic guanosine monophosphate–adenosine monophosphate synthase–stimulator of interferon genes (cGAS–STING) pathway, sensitizing the tumours to immune checkpoint blockade. Our findings support an immunological conversion strategy that uses nano-adjuvants to improve the effectiveness of immunotherapies for solid tumours.



中文翻译:

使用用于癌症免疫治疗的双特异性纳米生物偶联物对实体瘤进行免疫学转化

实体瘤对免疫疗法的反应有限。相比之下,与实体瘤相比,血液恶性肿瘤对免疫疗法的反应率要高得多。在几种微环境和生物学差异中,独特免疫调节分子的差异表达对血癌细胞与免疫细胞的相互作用有显着影响。信号淋巴细胞激活分子家族成员 7 (SLAMF7) 的自身配体受体是一种对促进机体先天免疫细胞检测和吞噬癌细胞至关重要的分子,几乎只在血液肿瘤的细胞表面表达,但不在固体上。在这里,我们展示了一种能够在实体瘤表面装饰 SLAMF7 的双特异性纳米生物偶联物诱导强大的吞噬作用并激活吞噬细胞环磷酸鸟苷-磷酸腺苷合酶-干扰素基因刺激物 (cGAS-STING) 通路,使肿瘤对免疫敏感检查站封锁。我们的研究结果支持一种免疫转化策略,该策略使用纳米佐剂来提高实体瘤免疫疗法的有效性。

更新日期:2022-11-11
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