Background The Tumor Microenviroment (TME) is a complex milieu that is increasingly recognized as a key factor in multiple stages of disease progression and responses to therapy as well as escape from immune surveillance. However, the precise contribution of specific immune effector and immune suppressor components of the TME in Burkitt lymphoma (BL) remains poorly understood. Methods In this paper, we applied the computational algorithm CIBERSORT to Gene Expression Profiling (GEP) datasets of 40 BL samples to draw a map of immune and stromal components of TME. Furthermore, by multiple immunohistochemistry (IHC) and multispectral immunofluorescence (IF), we investigated the TME of additional series of 40 BL cases to evaluate the role of the Programmed Death-1 and Programmed Death Ligand-1 (PD-1/PD-L1) immune checkpoint axis. Results Our results indicate that M2 polarized macrophages are the most prominent TME component in BL. In addition, we investigated the correlation between PD-L1 and latent membrane protein-2A (LMP2A) expression on tumour cells, highlighting a subgroup of BL cases characterized by a non-canonical latency program of EBV with an activated PD-L1 pathway. Conclusion In conclusion, our study analysed the TME in BL and identified a tolerogenic immune signature highlighting new potential therapeutic targets.

中文翻译：

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Burkitt 淋巴瘤的免疫景观揭示了 M2 巨噬细胞极化以及 PD-L1 表达与非经典 EBV 潜伏期程序之间的相关性

背景 肿瘤微环境 (TME) 是一个复杂的环境，越来越多地被认为是疾病进展和对治疗的反应以及逃避免疫监视的多个阶段的关键因素。然而，在伯基特淋巴瘤 (BL) 中，TME 的特定免疫效应和免疫抑制成分的确切贡献仍然知之甚少。方法 在本文中，我们将计算算法 CIBERSORT 应用于 40 个 BL 样本的基因表达谱 (GEP) 数据集，以绘制 TME 的免疫和基质成分图谱。此外，通过多重免疫组织化学 (IHC) 和多光谱免疫荧光 (IF)，我们研究了另外一系列 40 例 BL 病例的 TME，以评估 Programmed Death-1 和 Programmed Death Ligand-1 (PD-1/PD-L1) 的作用) 免疫检查点轴。结果 我们的结果表明，M2 极化巨噬细胞是 BL 中最突出的 TME 成分。此外，我们研究了肿瘤细胞上 PD-L1 和潜伏膜蛋白-2A (LMP2A) 表达之间的相关性，突出了以激活 PD-L1 通路的 EBV 的非典型潜伏程序为特征的 BL 病例亚组。结论 总之，我们的研究分析了 BL 中的 TME，并确定了一个耐受性免疫特征，突出了新的潜在治疗靶点。