INSERM U1053, Team 3 Oncogenesis of Cutaneous Lymphomas.
Pathology Department.
Am J Surg Pathol. 2018 Mar;42(3):326-334. doi: 10.1097/PAS.0000000000000983.
As checkpoint molecules' inhibition may represent a therapeutic option in relapsing cases, we assessed programmed death ligands' (PD-L1/PD-L2) expression in a series of 29 primary cutaneous diffuse large B-cell lymphoma, leg-type (PCDLBCL-LT) cases. Double immunostaining for either PD-L1 or PD-L2 was associated either with PAX5 staining to evaluate tumor cells or with CD68 or CD163 staining for macrophages. The microenvironment of PCDLBCL-LT was characterized by immunostainings for CD3 (tumor-infiltrating lymphocytes), FOXP3 (regulatory T cells), programmed cell death-1, and CD33 (myeloid-derived suppressor cells). The 9p24.1 locus encoding for PD-L1/PD-L2 was evaluated by fluorescence in situ hybridization. A PD-L1 expression was observed in all cases. However, double staining with PD-L1/PAX5 identified only 1 case harboring PD-L1 expression by tumor cells. All cases displayed PD-L1 expression by numerous immune cells, characterized as CD68 CD163 M2 macrophages. A normal fluorescence in situ hybridization pattern was observed in 21 of 26 cases. Three cases (11.5%) harbored a low polysomy status including the case with PD-L1 expression by tumor cells. Interestingly, 2 cases (7.7%) exhibited a PD-L1/PD-L2 locus break-apart pattern, and PD-L2 expression by tumor cells was observed. PD-L2 expression by tumor cells was not observed in the 24 cases without 9p24.1 rearrangement. Treating patients with relapsing PCDLBCL-LT by using immune checkpoint inhibitors may have an indirect effect through immune cells, except in rare cases with 9p24.1 rearrangement leading to PD-L2 expression by tumor cells. Reprogramming tumor-associated macrophages with anticancer therapies is appealing in such lymphoma subtypes wherein M2 macrophages represent the majority of immune cells.
作为检查点分子抑制可能代表复发病例的一种治疗选择，我们评估了 29 例原发性皮肤弥漫性大 B 细胞淋巴瘤，腿型（PCDLBCL-LT）病例中程序性死亡配体（PD-L1/PD-L2）的表达。PD-L1 或 PD-L2 的双重免疫染色与 PAX5 染色相结合，以评估肿瘤细胞，或与 CD68 或 CD163 染色相结合，以评估巨噬细胞。PCDLBCL-LT 的微环境通过 CD3（肿瘤浸润淋巴细胞）、FOXP3（调节性 T 细胞）、程序性细胞死亡-1 和 CD33（髓源性抑制细胞）的免疫染色来表征。9p24.1 基因座编码 PD-L1/PD-L2 通过荧光原位杂交进行评估。所有病例均观察到 PD-L1 表达。然而，PD-L1/PAX5 的双重染色仅在 1 例肿瘤细胞中发现 PD-L1 表达的病例中发现。所有病例均显示大量免疫细胞表达 PD-L1，其特征为 CD68 CD163 M2 巨噬细胞。在 26 例中的 21 例中观察到正常的荧光原位杂交模式。3 例（11.5%）存在低多倍体状态，包括肿瘤细胞中 PD-L1 表达的病例。有趣的是，2 例（7.7%）表现出 PD-L1/PD-L2 基因座分离模式，并且观察到肿瘤细胞中 PD-L2 的表达。在没有 9p24.1 重排的 24 例中未观察到肿瘤细胞中 PD-L2 的表达。用免疫检查点抑制剂治疗复发性 PCDLBCL-LT 的患者可能会通过免疫细胞产生间接影响，除非极少数情况下存在导致肿瘤细胞中 PD-L2 表达的 9p24.1 重排。用抗癌疗法重新编程肿瘤相关巨噬细胞在这种淋巴瘤亚型中很有吸引力，其中 M2 巨噬细胞代表大多数免疫细胞。
