美国外科病理学杂志 | 原发皮肤弥漫大B细胞淋巴瘤的肿瘤微环境和检查点分子——新治疗靶点

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  20%至70%的系统性弥漫大B细胞淋巴瘤(diffuse large B cell lymphomas,sDLBCLs)表达程序性死亡分子配体1(programmed death ligand 1,PD-L1)。然而,PD-L1在原发皮肤弥漫大B细胞淋巴瘤(primary cutaneous diffuse large B cell lymphoma,pcDLBCL)中的表达迄今尚无研究。本文研究了16例石蜡包埋的pcDLBCL组织样本[13例腿型(leg type,LT),3例其他类型(others type,OT)]中PD-1、PD-L1和CD33的表达,以及肿瘤微环境中的细胞构成,主要关注的是髓源性抑制细胞(myeloid-derived suppressor cell,MDSC)和肿瘤相关巨噬细胞。尽管表达程度存在差异(平均19.9%),所有样本均查见肿瘤细胞表达膜结合型PD-L1。正如预期,大多数DLBCL-LT(10例)为活化B细胞样型,其PD-L1分数为21.9%,高于生发中心B 细胞样型(7.7%)。肿瘤周围浸润的细胞主要为CD163(+)M2型巨噬细胞而非CD68(+)巨噬细胞(CD68:CD163=1:4~6),并混有相当比例共表达PD-L1的CD33(+)MDSC。肿瘤细胞不同程度地表达CD33(2%~60%)。MDSC或者M2巨噬细胞的数量与pcDLBCL的亚型(LT或OT)无关。T细胞仅占肿瘤微环境中的一小部分。我们认为,PD-L1(+)肿瘤细胞PD-L1(+)
MDSC可以抵抗PD-1(+)肿瘤浸润淋巴细胞(Tumor-infiltrating lymphocytes,TILs),进而导致TILs的抑制和减少。除此之外,我们发现M2巨噬细胞的极化现象,可能促成DLBCL患者的不良预后。因此,用抗PD-1/抗PD-L1或者抗CD33抗体,靶向肿瘤细胞和MDSC,可能成为治疗这种具有侵袭性的皮肤B 细胞淋巴瘤有价值的新方法。
来源:Am J Surg Pathol 2017;41:1267–1274
美国外科病理学杂志中文版2017年第一期摘要No.3
(李琳琳 翻译;刘慧 审校)

  The American Journal of Surgical Pathology中文版声明:
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