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.

Jesinghaus, Moritz; Steiger, Katja; Slotta-Huspenina, Julia; Drecoll, Enken; Pfarr, Nicole; Meyer, Petra; Konukiewitz, Björn; Bettstetter, Marcus; Wieczorek, Kathrin; Ott, Katja; Feith, Markus; Langer, Rupert; Weichert, Wilko; Specht, Katja; Boxberg, Melanie (2017). 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. OncoTarget, 8(29), pp. 46756-46768. Impact Journals LLC 10.18632/oncotarget.18606

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Service Sector > Institute of Pathology
04 Faculty of Medicine > Service Sector > Institute of Pathology > Clinical Pathology

UniBE Contributor:

Langer, Rupert

Subjects:

500 Science > 570 Life sciences; biology
600 Technology > 610 Medicine & health

ISSN:

1949-2553

Publisher:

Impact Journals LLC

Language:

English

Submitter:

Rupert Langer

Date Deposited:

17 Nov 2017 13:38

Last Modified:

27 Oct 2019 15:33

Publisher DOI:

10.18632/oncotarget.18606

PubMed ID:

28657901

Uncontrolled Keywords:

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

BORIS DOI:

10.7892/boris.106276

URI:

https://boris.unibe.ch/id/eprint/106276

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