Research Papers: Pathology:

Increased intraepithelial CD3+ T-lymphocytes and high PD-L1 expression on tumor cells are associated with a favorable prognosis in esophageal squamous cell carcinoma and allow prognostic immunogenic subgrouping

Moritz Jesinghaus _, Katja Steiger, Julia Slotta-Huspenina, Enken Drecoll, Nicole Pfarr, Petra Meyer, Björn Konukiewitz, Marcus Bettstetter, Kathrin Wieczorek, Katja Ott, Markus Feith, Rupert Langer, Wilko Weichert, Katja Specht and Melanie Boxberg

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Oncotarget. 2017; 8:46756-46768. https://doi.org/10.18632/oncotarget.18606

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Moritz Jesinghaus1,7, Katja Steiger1, Julia Slotta-Huspenina1, Enken Drecoll1, Nicole Pfarr1, Petra Meyer1, Björn Konukiewitz1, Marcus Bettstetter2, Kathrin Wieczorek3, Katja Ott4, Markus Feith5, Rupert Langer6, Wilko Weichert1,7, Katja Specht1 and Melanie Boxberg1

1 Institute of Pathology, Technical University of Munich, Munich, Germany

2 Molecular Pathology South-Bavaria, Munich, Germany

3 Institute of Pathology, University of Heidelberg, Heidelberg, Germany

4 RoMED Surgical Clinic, Rosenheim, Germany

5 Department of Surgery, Technical University of Munich, Munich, Germany

6 Institute of Pathology, University of Bern, Bern, Switzerland

7 German Cancer Consortium, Partner Site Munich, Munich, Germany

Correspondence to:

Moritz Jesinghaus, email:

Melanie Boxberg, email:

Keywords: esophageal squamous cell carcinoma, immunologic microenvironment, PD-L1, tumor infiltrating lymphocytes, intraepithelial CD3, Pathology Section

Received: April 11, 2017 Accepted: May 08, 2017 Published: June 22, 2017


Esophageal squamous cell carcinoma (ESCC) is the most common esophageal cancer associated with poor prognosis and additional therapeutic strategies must be implemented to optimize ESCC treatment. Meanwhile, the important biologic role and potential prognostic and therapeutic implications of a tumors immunologic microenvironment (IM) have been recognized in various cancers.

In order to investigate the contexture and the prognostic relevance of the IM in ESCC, we immunohistochemically evaluated the extent of overall/intraepithelial TILs (CD3+/CD8+) and of PD-1 / PD-L1 expression in a cohort of 125 therapy-naive ESCCs, additionally assessing PD-L1 copy number status via fluorescence in-situ hybridization.

High intraepithelial CD3+ TILs (CD3ihigh) and high PD-L1 expression on tumor cells (PD-L1high) were each significantly associated with improved overall- (OS) (CD3+: p = 0.019; PD-L1: p = 0.028), disease specific- (DSS) (CD3+: p = 0.05; PD-L1: p = 0.006) and disease free survival (DFS) (CD3+: p = 0.009; PD-L1: p < 0.001). CD3ihigh- and PD-L1high cases were significantly associated with one another (p < 0.001). Subgrouping of ESCC revealed decreased OS (p = 0.031), DSS (p = 0.012) and DFS (p < 0.001) for CD3ilow/PD-L1low cancers.

Our data not only associate CD3ihigh- and PD-L1high ESCC with a beneficial outcome, but also demonstrate PD-L1high- and CD3ihigh status to be closely intertwined. Furthermore, our study demarcates a prognostically unfavorable, “non-immunoreactive” CD3ilow / PD-L1low ESCC-subgroup, potentially forming the basis for an immune-based stratification of ESCC.

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