Replication Study: The CD47-signal regulatory protein alpha (SIRPa) interaction is a therapeutic target for human solid tumors
Replication Study: The CD47-signal regulatory protein alpha (SIRPa) interaction is a therapeutic target for human solid tumors
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DOI：
10.7554/elife.18173
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发表时间：
2017-01-19
期刊：
影响因子：
7.7
通讯作者：
Horrigan, Stephen K.
中科院分区：
文献类型：
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作者：
Horrigan, Stephen K.
2015年，作为生殖项目：癌症生物学的一部分，我们发表了一份注册报告（Chroomski等人，2015），其描述了我们打算如何复制来自该论文的所选实验。CD 47-信号调节蛋白α（SIRPa）相互作用是人实体瘤的治疗靶标（威灵厄姆等人，2012年）。在这里，我们报告这些实验的结果。我们发现，与对照组相比，用抗小鼠CD 47抗体治疗携带原位乳腺肿瘤的免疫活性小鼠会导致短期贫血，这与之前描述的CD 47在衰老红细胞正常吞噬中的功能以及原始研究中报告的结果一致（表S4;威灵厄姆等人，2012年）。在施用抗-CD 47抗体或IgG同种型对照30天后，未发现肿瘤重量有统计学差异，而原始研究报道了抗-CD 47治疗对肿瘤生长的抑制（图6A，B;威灵厄姆等人，2012年）。然而，我们重复这个实验的努力被混淆了，因为在几只小鼠中发生了肿瘤的自发消退。此外，对切除的肿瘤进行炎性细胞浸润评分。我们发现IgG和抗CD 47处理的肿瘤导致最小至中度的淋巴细胞浸润，而最初的研究观察到IgG处理的肿瘤中的稀疏淋巴细胞浸润和抗CD 47处理的肿瘤中的炎性细胞浸润增加（图6C;威灵厄姆等人，2012年）。此外，我们观察到，与IgG对照相比，抗CD 47处理的肿瘤中嗜中性粒细胞浸润略微增加。最后，我们报告了一个荟萃分析的结果。
In 2015, as part of the Reproducibility Project: Cancer Biology, we published a Registered Report (Chroscinski et al., 2015) that described how we intended to replicate selected experiments from the paper The CD47-signal regulatory protein alpha (SIRPa) interaction is a therapeutic target for human solid tumors (Willingham et al., 2012). Here we report the results of those experiments. We found that treatment of immune competent mice bearing orthotopic breast tumors with anti-mouse CD47 antibodies resulted in short-term anemia compared to controls, consistent with the previously described function of CD47 in normal phagocytosis of aging red blood cells and results reported in the original study (Table S4; Willingham et al., 2012). The weight of tumors after 30 days administration of anti-CD47 antibodies or IgG isotype control were not found to be statistically different, whereas the original study reported inhibition of tumor growth with anti-CD47 treatment (Figure 6A,B; Willingham et al., 2012). However, our efforts to replicate this experiment were confounded because spontaneous regression of tumors occurred in several of the mice. Additionally, the excised tumors were scored for inflammatory cell infiltrates. We found IgG and anti-CD47 treated tumors resulted in minimal to moderate lymphocytic infiltrate, while the original study observed sparse lymphocytic infiltrate in IgG-treated tumors and increased inflammatory cell infiltrates in anti-CD47 treated tumors (Figure 6C; Willingham et al., 2012). Furthermore, we observed neutrophilic infiltration was slightly increased in anti-CD47 treated tumors compared to IgG control. Finally, we report a meta-analysis of the result.