Post-transplant lymphoproliferative disorders (PTLD) occur after solid organ transplantation (SOT) or hematopoietic stem cell transplantation (HCT) and are frequently associated with Epstein-Barr virus (EBV). Because of the complex immune setup in PTLD patients, the tumor microenvironment (TME) is of particular interest to understand PTLD pathogenesis and elucidate predictive factors and possible treatment options. We present a comparative study of clinicopathological features of 48 PTLD after HCT (n = 26) or SOT (n = 22), including non-destructive (n = 6), polymorphic (n = 23), and monomorphic (n = 18) PTLD and classic Hodgkin lymphoma (n = 1). EBV was positive in 35 cases (73%). A detailed examination of the TME with image analysis-based quantification in 22 cases revealed an inflammatory TME despite underlying immunosuppression and significant differences in its density and composition depending on type of transplant, PTLD subtypes, and EBV status. Tumor-associated macrophages (TAMs) expressing CD163 (p = 0.0022) and Mannose (p = 0.0016) were enriched in PTLD after HCT. Double stains also showed differences in macrophage polarization, with more frequent M1 polarization after HCT (p = 0.0321). Higher counts for TAMs (CD163 (p = 0.0008) and cMaf (p = 0.0035)) as well as in the T cell compartment (Granzyme B (p = 0.0028), CD8 (p = 0.01), and for PD-L1 (p = 0.0305)) were observed depending on EBV status. In conclusion, despite the presence of immunosuppression, PTLD predominantly contains an inflammatory TME characterized by mostly M1-polarized macrophages and cytotoxic T cells. Status post HCT, EBV positivity, and polymorphic subtype are associated with an actively inflamed TME, indicating a specific response of the immune system. Further studies need to elucidate prognostic significance and potential therapeutic implications of the TME in PTLD.

实体器官移植（SOT）或造血干细胞移植（HCT）后发生移植后淋巴细胞增生性疾病（PTLD），并经常与爱泼斯坦-巴尔病毒（EBV）相关。由于PTLD患者的免疫系统很复杂，因此特别需要了解肿瘤微环境（TME），以了解PTLD的发病机理并阐明预测因素和可能的治疗选择。我们对HCT（n = 26）或SOT（n = 22）后48 PTLD的临床病理特征进行比较研究，包括非破坏性（n = 6），多态性（n = 23）和单态性（n = 18）。 PTLD和经典霍奇金淋巴瘤（n= 1）。EBV阳性35例（73％）。通过基于图像分析的定量方法对TME进行了详细检查，发现22例患者存在炎症性TME，尽管存在潜在的免疫抑制作用，并且其密度和组成存在显着差异，具体取决于移植类型，PTLD亚型和EBV状态。HCT后，表达CD163（p = 0.0022）和甘露糖（p = 0.0016）的肿瘤相关巨噬细胞（PTM）富含PTLD。双重染色还显示出巨噬细胞极化的差异，HCT后M1极化更为频繁（p = 0.0321）。TAM（CD163（p = 0.0008）和cMaf（p = 0.0035））以及T细胞区室（Granzyme B（p根据EBV的状态，观察到CD8（p = 0.018），CD8（p = 0.01）和PD-L1（p = 0.0305）。总之，尽管存在免疫抑制作用，但PTLD主要包含以大多数M1极化巨噬细胞和细胞毒性T细胞为特征的炎性TME。HCT，EBV阳性和多态性亚型后的状态与积极发炎的TME相关，表明免疫系统的特异性反应。进一步的研究需要阐明TME在PTLD中的预后意义和潜在的治疗意义。