Distribution of tumor-infiltrating-T-lymphocytes and possible tumor-escape mechanisms avoiding immune cell attack in locally advanced adenocarcinomas of the esophagus.
INTRODUCTION
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.


PATIENTS AND METHODS
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.


RESULTS
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.


DISCUSSION
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.
['Schoemmel|M|M|', 'Loeser|H|H|http://orcid.org/0000-0003-4555-1327', 'Kraemer|M|M|', 'Wagener-Ryczek|S|S|', 'Hillmer|A|A|', 'Bruns|C|C|', 'Thelen|M|M|', 'Schröder|W|W|', 'Zander|T|T|', 'Lechner|A|A|', 'Buettner|R|R|', 'Schlösser|H|H|', 'Gebauer|F|F|', 'Quaas|A|A|', '|||']
D000230:Adenocarcinoma D000368:Aged D060890:B7-H1 Antigen D015536:Down-Regulation D004938:Esophageal Neoplasms D005260:Female D015234:HLA-A Antigens D015235:HLA-B Antigens D006801:Humans D007111:Immunity, Cellular D007249:Inflammation D018655:Lymphocyte Count D016246:Lymphocytes, Tumor-Infiltrating D008297:Male D008875:Middle Aged D009361:Neoplasm Invasiveness D011379:Prognosis D013997:Time Factors D019139:Tumor Escape D059016:Tumor Microenvironment
Adenocarcinoma of the esophagus Inflammation PD-L1 MHC1 Computer applications software