Schoemmel M, Loeser H, Kraemer M, Wagener-Ryczek S, Hillmer A, Bruns C, Thelen M, Schröder W, Zander T, Lechner A, Buettner R, Schlösser H, Gebauer F, Quaas A
Institute of Pathology, University-Hospital of Cologne, University of Cologne, Kerpener Strasse 62, 50937, Cologne, Germany.
Department of General, Visceral and Cancer Surgery, University of Cologne, Cologne, Germany.
Clin Transl Oncol. 2021 Aug;23(8):1601-1610. doi: 10.1007/s12094-021-02556-2. Epub 2021 Feb 10.
The inflammatory microenvironment has emerged as one of the focuses of cancer research. Little is known about the immune environment in esophageal adenocarcinoma (EAC) and possible tumor-escape mechanisms to avoid immune cell attack.
We measured T cell inflammation (CD3, CD8) in the microenvironment using a standardized software-based evaluation algorithm considering different predefined tumor areas as well as expression of MHC class 1 and PD-L1 on 75 analyzable primarily resected and locally advanced (≥ pT2) EACs. We correlated these findings statistically with clinical data.
Patients with high amounts of T cell infiltration in their tumor center showed a significant survival benefit of 41.4 months compared to 16.3 months in T cell poor tumors (p = 0.025), although CD3 fails to serve as an independent prognostic marker in multivariate analysis. For the invasion zone, a correlation between number of T-cells and overall survival was not detectable. Loss of MHC1 protein expression on tumor cells was seen in 32% and PD-L1 expression using the combined positive score (CPS) in 21.2%. Most likely due to small numbers of cases, both markers are not prognostically relevant, even though PD-L1 expression correlates with advanced tumor stages.
Our analyses reveal an outstanding, though not statistically independent, prognostic relevance of T-cell-rich inflammation in our group of EACs, in particular driven by the tumor center. For the first time, we describe that the inner part of the invasion zone in EACs shows significantly fewer T-cells than other tumor segments and is prognostically irrelevant. We also demonstrate that the loss of antigen presenting ability via MHC1 downregulation by the carcinoma cells is a common escape mechanism in EACs. Future work will need to show whether tumors with MHC class 1 loss respond less well to immunotherapy.
炎症微环境已成为癌症研究的重点之一。关于食管腺癌（EAC）中的免疫环境以及避免免疫细胞攻击的可能肿瘤逃逸机制，我们所知甚少。
我们使用基于软件的标准化评估算法，在微环境中测量T细胞炎症（CD3、CD8），该算法考虑了不同的预定义肿瘤区域，以及75例可分析的原发性切除和局部晚期（≥pT2）EAC中MHC 1类和PD-L1的表达。我们将这些发现与临床数据进行了统计学关联。
肿瘤中心T细胞浸润量高的患者显示出显著的生存获益，中位生存期为41.4个月，而T细胞浸润少的肿瘤患者为16.3个月（p = 0.025），尽管在多变量分析中CD3不能作为独立的预后标志物。对于浸润区，未检测到T细胞数量与总生存期之间的相关性。32%的肿瘤细胞出现MHC1蛋白表达缺失，使用联合阳性评分（CPS）时PD-L1表达为21.2%。很可能由于病例数较少，这两个标志物均无预后相关性，尽管PD-L1表达与肿瘤晚期相关。
我们的分析揭示了在我们的EAC队列中，富含T细胞的炎症具有显著的预后相关性，尽管在统计学上不独立，尤其是由肿瘤中心驱动。我们首次描述，EAC浸润区内部的T细胞明显少于其他肿瘤节段，且无预后相关性。我们还证明，癌细胞通过下调MHC1导致抗原呈递能力丧失是EAC中常见的逃逸机制。未来的研究需要表明，MHC 1缺失的肿瘤对免疫治疗的反应是否较差。
