Resumen de Distribution of tumor‑infltrating‑T‑lymphocytes and possible tumor‑escape mechanisms avoiding immune cell attack in locally advanced adenocarcinomas of the esophagus
M. Schoemmel, H. Loeser, M. Kraemer, S. Wagener Ryczek, A. Hillmer, C. Bruns, M. Thelen, W. Schröder, T. Zander, R. Buettner
Introduction The infammatory 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.
Patients and methods We measured T cell infammation (CD3, CD8) in the microenvironment using a standardized softwarebased evaluation algorithm considering diferent predefned 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 fndings statistically with clinical data.
Results Patients with high amounts of T cell infltration in their tumor center showed a signifcant survival beneft 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.
Discussion Our analyses reveal an outstanding, though not statistically independent, prognostic relevance of T-cell-rich infammation in our group of EACs, in particular driven by the tumor center. For the frst time, we describe that the inner part of the invasion zone in EACs shows signifcantly 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
