Universität zu Köln

Lechner, Axel, Schloesser, Hans, Rothschild, Sacha I., Thelen, Martin ORCID: 0000-0002-2785-9726, Reuter, Sabrina, Zentis, Peter, Shimabukuro-Vornhagen, Alexander, Theurich, Sebastian ORCID: 0000-0001-5706-8258, Wennhold, Kerstin ORCID: 0000-0001-5539-7226, Garcia-Marquez, Maria, Tharun, Lars, Quaas, Alexander, Schauss, Astrid, Isensee, Joerg ORCID: 0000-0002-3390-0051, Hucho, Tim ORCID: 0000-0002-4147-9308, Huebbers, Christian ORCID: 0000-0002-2934-1218, von Bergwelt-Baildon, Michael and Beutner, Dirk (2017). Characterization of tumor-associated T-lymphocyte subsets and immune checkpoint molecules in head and neck squamous cell carcinoma. Oncotarget, 8 (27). S. 44418 - 44434. ORCHARD PARK: IMPACT JOURNALS LLC. ISSN 1949-2553

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Abstract

The composition of tumor-infiltrating lymphocytes (TIL) reflects biology and immunogenicity of cancer. Here, we characterize T-cell subsets and expression of immune checkpoint molecules in head and neck squamous cell carcinoma (HNSCC). We analyzed TIL subsets in primary tumors (n = 34), blood (peripheral blood mononuclear cells (PBMC); n = 34) and non-cancerous mucosa (n = 7) of 34 treatment-naive HNSCC patients and PBMC of 15 healthy controls. Flow cytometry analyses revealed a highly variable T-cell infiltration mainly of an effector memory phenotype (CD45RA(-)/CCR7(-)). Naive T cells (CD45RA(+)/CCR7(+)) were decreased in the microenvironment compared to PBMC of patients, while regulatory T cells (CD4(+)/CD25(+)/CD127(low) and CD4(+)/CD39(+)) were elevated. Furthermore, we performed digital image analyses of entire cross sections of HNSCC to define the 'Immunoscore' (CD3(+) and CD8(+) cell infiltration in tumor core and invasive margin) and quantified MHC class I expression on tumor cells by immunohistochemistry. Immune checkpoint molecules cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), programmed cell death 1 (PD-1) and programmed cell death 1 ligand 1 (PD-L1) were increased in TILs compared to peripheral T cells in flow-cytometric analysis. Human papillomavirus (HPV) positive tumors showed higher numbers of TILs, but a similar composition of T-cell subsets and checkpoint molecule expression compared to HPV negative tumors. Taken together, the tumor microenvironment of HNSCC is characterized by a strong infiltration of regulatory T cells and high checkpoint molecule expression on T-cell subsets. In view of increasingly used immunotherapies, a detailed knowledge of TILs and checkpoint molecule expression on TILs is of high translational relevance.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Lechner, Axel UNSPECIFIED UNSPECIFIED UNSPECIFIED Schloesser, Hans UNSPECIFIED UNSPECIFIED UNSPECIFIED Rothschild, Sacha I. UNSPECIFIED UNSPECIFIED UNSPECIFIED Thelen, Martin UNSPECIFIED orcid.org/0000-0002-2785-9726 UNSPECIFIED Reuter, Sabrina UNSPECIFIED UNSPECIFIED UNSPECIFIED Zentis, Peter UNSPECIFIED UNSPECIFIED UNSPECIFIED Shimabukuro-Vornhagen, Alexander UNSPECIFIED UNSPECIFIED UNSPECIFIED Theurich, Sebastian UNSPECIFIED orcid.org/0000-0001-5706-8258 UNSPECIFIED Wennhold, Kerstin UNSPECIFIED orcid.org/0000-0001-5539-7226 UNSPECIFIED Garcia-Marquez, Maria UNSPECIFIED UNSPECIFIED UNSPECIFIED Tharun, Lars UNSPECIFIED UNSPECIFIED UNSPECIFIED Quaas, Alexander UNSPECIFIED UNSPECIFIED UNSPECIFIED Schauss, Astrid UNSPECIFIED UNSPECIFIED UNSPECIFIED Isensee, Joerg UNSPECIFIED orcid.org/0000-0002-3390-0051 UNSPECIFIED Hucho, Tim UNSPECIFIED orcid.org/0000-0002-4147-9308 UNSPECIFIED Huebbers, Christian UNSPECIFIED orcid.org/0000-0002-2934-1218 UNSPECIFIED von Bergwelt-Baildon, Michael UNSPECIFIED UNSPECIFIED UNSPECIFIED Beutner, Dirk UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-225166
DOI:	10.18632/oncotarget.17901
Journal or Publication Title:	Oncotarget
Volume:	8
Number:	27
Page Range:	S. 44418 - 44434
Date:	2017
Publisher:	IMPACT JOURNALS LLC
Place of Publication:	ORCHARD PARK
ISSN:	1949-2553
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language CLASS-I EXPRESSION; INFILTRATING LYMPHOCYTES; HUMAN-PAPILLOMAVIRUS; PERIPHERAL-BLOOD; LUNG-CANCER; COLORECTAL-CANCER; DOWN-REGULATION; SURVIVAL; EXHAUSTION; NIVOLUMAB Multiple languages Oncology; Cell Biology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/22516