Department of Hematology, University of Groningen, University Medical Center Groningen (UMCG), Groningen, GZ, 9713, The Netherlands.
Department of Medical Oncology, University of Groningen, University Medical Center Groningen (UMCG), Groningen, GZ, 9713, The Netherlands.
Nat Commun. 2019 Feb 1;10(1):533. doi: 10.1038/s41467-018-08013-z.
CD47 is a prominent new target in cancer immunotherapy, with antagonistic antibodies currently being evaluated in clinical trials. For effective evaluation of this strategy it is crucial to identify which patients are suited for CD47-targeted therapy. In this respect, expression of the pro-phagocytic signal SLAMF7 on both macrophages and cancer cells was recently reported to be a requisite for CD47 antibody-mediated phagocytosis. Here, we demonstrate that in fact SLAMF7 expression on cancer cells is not required and does not impact on CD47 antibody therapy. Moreover, SLAMF7 also does not impact on phagocytosis induction by CD20 antibody rituximab nor associates with overall survival of Diffuse Large B-Cell Lymphoma patients. In contrast, expression of CD47 negatively impacts on overall and progression free survival. In conclusion, cancer cell expression of SLAMF7 is not required for phagocytosis and, in contrast to CD47 expression, should not be used as selection criterion for CD47-targeted therapy.
CD47 是癌症免疫疗法中的一个重要新靶点，目前有拮抗抗体正在临床试验中进行评估。为了有效评估这一策略，确定哪些患者适合 CD47 靶向治疗至关重要。在这方面，最近有研究报道，巨噬细胞和癌细胞表面表达吞噬信号 SLAMF7 是 CD47 抗体介导吞噬作用所必需的。在这里，我们证明事实上癌细胞表面的 SLAMF7 表达并非必需，也不会影响 CD47 抗体治疗。此外，SLAMF7 也不会影响 CD20 抗体利妥昔单抗诱导的吞噬作用，也与弥漫性大 B 细胞淋巴瘤患者的总生存率无关。相反，CD47 的表达会对总生存期和无进展生存期产生负面影响。总之，癌细胞表面 SLAMF7 的表达不是吞噬作用所必需的，与 CD47 表达相反，不应作为 CD47 靶向治疗的选择标准。
