Department of Neurosurgery, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Brain Tumor Center, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Nat Nanotechnol. 2022 Dec;17(12):1332-1341. doi: 10.1038/s41565-022-01245-7. Epub 2022 Nov 10.
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.
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液癌细胞与免疫细胞的相互作用有重要贡献。信号淋巴细胞激活分子家族成员 7（SLAMF7）的自我配体受体是一种促进机体固有免疫细胞检测和吞噬癌细胞的关键分子，几乎仅在血液肿瘤细胞的表面表达，而不在实体肿瘤上表达。在这里，我们展示了一种双特异性纳米生物缀合物，它能够在实体肿瘤表面修饰 SLAMF7，诱导强烈的吞噬作用，并激活吞噬细胞环鸟苷酸-腺苷酸单磷酸合酶-干扰素基因刺激物（cGAS-STING）途径，使肿瘤对免疫检查点阻断敏感。我们的研究结果支持一种免疫转化策略，即使用纳米佐剂来提高免疫疗法治疗实体瘤的效果。
