Universität zu Köln

Schoemmel, M., Loeser, H., Kraemer, M., Wagener-Ryczek, S., Hillmer, A., Bruns, C., Thelen, M., Schroeder, W., Zander, T., Lechner, A., Buettner, R., Schloesser, H., Gebauer, F. and Quaas, A. (2021). Distribution of tumor-infiltrating-T-lymphocytes and possible tumor-escape mechanisms avoiding immune cell attack in locally advanced adenocarcinomas of the esophagus. Clin. Transl. Oncol., 23 (8). S. 1601 - 1611. CHAM: SPRINGER INT PUBL AG. ISSN 1699-3055

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Abstract

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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Schoemmel, M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Loeser, H. UNSPECIFIED UNSPECIFIED UNSPECIFIED Kraemer, M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Wagener-Ryczek, S. UNSPECIFIED UNSPECIFIED UNSPECIFIED Hillmer, A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Bruns, C. UNSPECIFIED UNSPECIFIED UNSPECIFIED Thelen, M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Schroeder, W. UNSPECIFIED UNSPECIFIED UNSPECIFIED Zander, T. UNSPECIFIED UNSPECIFIED UNSPECIFIED Lechner, A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Buettner, R. UNSPECIFIED UNSPECIFIED UNSPECIFIED Schloesser, H. UNSPECIFIED UNSPECIFIED UNSPECIFIED Gebauer, F. UNSPECIFIED UNSPECIFIED UNSPECIFIED Quaas, A. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-572645
DOI:	10.1007/s12094-021-02556-2
Journal or Publication Title:	Clin. Transl. Oncol.
Volume:	23
Number:	8
Page Range:	S. 1601 - 1611
Date:	2021
Publisher:	SPRINGER INT PUBL AG
Place of Publication:	CHAM
ISSN:	1699-3055
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language PROGNOSTIC-SIGNIFICANCE; COLORECTAL-CANCER; GASTRIC-CANCER; CLASS-I; EXPRESSION; SURVIVAL Multiple languages Oncology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/57264