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Combination of CD47 and signal-regulatory protein-α constituting the "don't eat me signal" is a prognostic factor in diffuse large B-cell lymphoma.
Cancer Science ( IF 4.5 ) Pub Date : 2020-04-28 , DOI: 10.1111/cas.14437 Ryo Kazama 1, 2 , Hiroaki Miyoshi 1 , Mai Takeuchi 1 , Kohta Miyawaki 1, 3 , Kazutaka Nakashima 1 , Noriaki Yoshida 1, 4 , Keisuke Kawamoto 5 , Eriko Yanagida 1 , Kyohei Yamada 1 , Takeshi Umeno 1 , Takaharu Suzuki 1, 5 , Koji Kato 3 , Jun Takizawa 5 , Masao Seto 1 , Koichi Akashi 3 , Koichi Ohshima 1
Cancer Science ( IF 4.5 ) Pub Date : 2020-04-28 , DOI: 10.1111/cas.14437 Ryo Kazama 1, 2 , Hiroaki Miyoshi 1 , Mai Takeuchi 1 , Kohta Miyawaki 1, 3 , Kazutaka Nakashima 1 , Noriaki Yoshida 1, 4 , Keisuke Kawamoto 5 , Eriko Yanagida 1 , Kyohei Yamada 1 , Takeshi Umeno 1 , Takaharu Suzuki 1, 5 , Koji Kato 3 , Jun Takizawa 5 , Masao Seto 1 , Koichi Akashi 3 , Koichi Ohshima 1
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The interaction between CD47 and signal‐regulatory protein‐α (SIRPα) inhibits phagocytosis, thus affecting the clinical outcomes of neoplastic diseases. Although CD47 upregulation is associated with poor prognosis in several malignancies, the effect of SIRPα expression and its coexpression with CD47 remains unclear. This study aimed to investigate the clinicopathologic effect of CD47 and SIRPα expression in diffuse large B‐cell lymphoma (DLBCL). Immunostaining of 120 biopsy samples showed that CD47 is primarily expressed in tumor cells, whereas SIRPα is expressed in nonneoplastic stromal cells, mostly macrophages. CD47high cases showed higher MYC protein expression and lower MYC translocation. The SIRPαhigh cases presented significantly shorter overall survival (OS) and progression‐free survival (PFS) than SIRPαlow cases in the activated B‐cell (ABC) subtype of DLBCL (P = .04 and P = .02, respectively). Both CD47high and SIRPαhigh presented significantly shorter OS and PFS than other cases among all DLBCL patients (P = .01 and P = .004, respectively), and the ABC type (P = .04 and P = .008, respectively) but not the germinal center B‐cell type. Both CD47high and SIRPαhigh yielded a constant independent prognostic value for OS and PFS in multivariate analysis (hazard ratio [HR], 2.93; 95% confidence interval [CI], 1.20‐7.43; P = .02; and HR, 2.87; 95% CI, 1.42‐5.85; P = .003, respectively). To the best of our knowledge, this is the first study to report that combinatorial CD47 and SIRPα expression is a potential independent prognostic factor for DLBCL. Evaluation of CD47 and SIRPα expression could be useful before CD47 blockade therapy.
中文翻译：
CD47和信号调节蛋白-α的结合构成“不要吃我的信号”是弥漫性大B细胞淋巴瘤的预后因素。
CD47和信号调节蛋白-α（SIRPα）之间的相互作用抑制吞噬作用，从而影响肿瘤疾病的临床结局。尽管CD47的上调与一些恶性肿瘤的预后不良有关，但SIRPα表达及其与CD47的共表达的影响仍不清楚。本研究旨在探讨CD47和SIRPα表达在弥漫性大B细胞淋巴瘤（DLBCL）中的临床病理作用。对120个活检样本进行免疫染色显示，CD47主要在肿瘤细胞中表达，而SIRPα在非肿瘤性基质细胞（主要是巨噬细胞）中表达。高CD47病例显示更高的MYC蛋白表达和更低的MYC易位。SIRPα高在DLBCL的激活B细胞（ABC）亚型中，这些病例的总生存期（OS）和无进展生存期（PFS）比SIRPα低病例要短得多（分别为P = .04和P = .02）。在所有DLBCL患者中，CD47高和SIRPα高的OS和PFS明显短于其他病例（分别为P = .01和P = .004）和ABC类型（分别为P = .04和P = .008）但不是生发中心B细胞类型。CD47高和SIRPα高在多变量分析中得出OS和PFS的恒定独立预后值（危险比[HR]为2.93; 95％置信区间[CI]为1.20-7.43; P = .02; HR为2.87; 95％CI为1.42- 5.85；P 分别为0.003）。据我们所知，这是第一个报告组合CD47和SIRPα表达是DLBCL的潜在独立预后因素的研究。CD47和SIRPα表达的评估可能在CD47阻断治疗之前有用。
更新日期：2020-04-28
中文翻译：
CD47和信号调节蛋白-α的结合构成“不要吃我的信号”是弥漫性大B细胞淋巴瘤的预后因素。
CD47和信号调节蛋白-α（SIRPα）之间的相互作用抑制吞噬作用，从而影响肿瘤疾病的临床结局。尽管CD47的上调与一些恶性肿瘤的预后不良有关，但SIRPα表达及其与CD47的共表达的影响仍不清楚。本研究旨在探讨CD47和SIRPα表达在弥漫性大B细胞淋巴瘤（DLBCL）中的临床病理作用。对120个活检样本进行免疫染色显示，CD47主要在肿瘤细胞中表达，而SIRPα在非肿瘤性基质细胞（主要是巨噬细胞）中表达。高CD47病例显示更高的MYC蛋白表达和更低的MYC易位。SIRPα高在DLBCL的激活B细胞（ABC）亚型中，这些病例的总生存期（OS）和无进展生存期（PFS）比SIRPα低病例要短得多（分别为P = .04和P = .02）。在所有DLBCL患者中，CD47高和SIRPα高的OS和PFS明显短于其他病例（分别为P = .01和P = .004）和ABC类型（分别为P = .04和P = .008）但不是生发中心B细胞类型。CD47高和SIRPα高在多变量分析中得出OS和PFS的恒定独立预后值（危险比[HR]为2.93; 95％置信区间[CI]为1.20-7.43; P = .02; HR为2.87; 95％CI为1.42- 5.85；P 分别为0.003）。据我们所知，这是第一个报告组合CD47和SIRPα表达是DLBCL的潜在独立预后因素的研究。CD47和SIRPα表达的评估可能在CD47阻断治疗之前有用。
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