Universität zu Köln

Watermann, Christian ORCID: 0000-0002-6960-5863, Pasternack, Helen ORCID: 0000-0003-2386-2300, Idel, Christian, Ribbat-Idel, Julika, Braegelmann, Johannes, Kuppler, Patrick, Offermann, Anne, Jonigk, Danny, Kuehnel, Mark, Schroeck, Andreas, Dreyer, Eva, Rosero, Christian, Nathansen, Jacqueline, Dubrovska, Anna, Tharun, Lars, Kirfel, Jutta, Wollenberg, Barbara, Perner, Sven and Krupar, Rosemarie (2021). Recurrent HNSCC Harbor an Immunosuppressive Tumor Immune Microenvironment Suggesting Successful Tumor Immune Evasion. Clin. Cancer Res., 27 (2). S. 632 - 645. PHILADELPHIA: AMER ASSOC CANCER RESEARCH. ISSN 1557-3265

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Abstract

Purpose: Recurrent tumors (RT) of head and neck squamous cell carcinoma (HNSCC) occur in up to 60%, with poor therapeutic response and detrimental prognosis. We hypothesized that HNSCC RTs successfully evade antitumor immune response and aimed to reveal tumor immune microenvironment (TIME) changes of primary tumors (PT) and corresponding RTs. Experimental Design: Tumor-infiltrating leukocytes (TIL) of 300 PTs and 108 RTs from two large independent and clinically well-characterized HNSCC cohorts [discovery cohort (DC), validation cohort (VD)] were compared by IHC. mRNA expression analysis of 730 immune-related genes was performed for 18 PTs and RTs after adjuvant chemoradiotherapy (CRT). The effect of chemotherapy and radiation resistance was assessed with an in vitro spheroid/immunocyte coculture model. Results: TIME analysis revealed overall decrease of TILs with significant loss of CD8(+) T cells (DC P = 0.045/VC P < 0.0001) and B lymphocytes (DC P = 0.036/VC P < 0.0001) in RTs compared with PTs in both cohorts. Decrease predominantly occurred in RTs after CRT. Gene expression analysis confirmed loss of TILs (P = 0.0004) and B lymphocytes (P < 0.0001) and showed relative increase of neutrophils (P = 0.018), macrophages (P < 0.0001), dendritic cells (P = 0.0002), and mast cells (P = 0.0057) as well as lower overall expression of immune-related genes (P = 0.018) in RTs after CRT. Genes involved in B-lymphocyte functions and number of tertiary lymphoid structures showed the strongest decrease. SPP1 and MAPK1 were upregulated in vivo and in vitro, indicating their potential suitability as therapeutic targets in CRT resistance. Conclusions: HNSCC RTs have an immunosuppressive TIME, which is particularly apparent after adjuvant CRT and might substantially contribute to poor therapeutic response and prognosis.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Watermann, Christian UNSPECIFIED orcid.org/0000-0002-6960-5863 UNSPECIFIED Pasternack, Helen UNSPECIFIED orcid.org/0000-0003-2386-2300 UNSPECIFIED Idel, Christian UNSPECIFIED UNSPECIFIED UNSPECIFIED Ribbat-Idel, Julika UNSPECIFIED UNSPECIFIED UNSPECIFIED Braegelmann, Johannes UNSPECIFIED UNSPECIFIED UNSPECIFIED Kuppler, Patrick UNSPECIFIED UNSPECIFIED UNSPECIFIED Offermann, Anne UNSPECIFIED UNSPECIFIED UNSPECIFIED Jonigk, Danny UNSPECIFIED UNSPECIFIED UNSPECIFIED Kuehnel, Mark UNSPECIFIED UNSPECIFIED UNSPECIFIED Schroeck, Andreas UNSPECIFIED UNSPECIFIED UNSPECIFIED Dreyer, Eva UNSPECIFIED UNSPECIFIED UNSPECIFIED Rosero, Christian UNSPECIFIED UNSPECIFIED UNSPECIFIED Nathansen, Jacqueline UNSPECIFIED UNSPECIFIED UNSPECIFIED Dubrovska, Anna UNSPECIFIED UNSPECIFIED UNSPECIFIED Tharun, Lars UNSPECIFIED UNSPECIFIED UNSPECIFIED Kirfel, Jutta UNSPECIFIED UNSPECIFIED UNSPECIFIED Wollenberg, Barbara UNSPECIFIED UNSPECIFIED UNSPECIFIED Perner, Sven UNSPECIFIED UNSPECIFIED UNSPECIFIED Krupar, Rosemarie UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-601557
DOI:	10.1158/1078-0432.CCR-20-0197
Journal or Publication Title:	Clin. Cancer Res.
Volume:	27
Number:	2
Page Range:	S. 632 - 645
Date:	2021
Publisher:	AMER ASSOC CANCER RESEARCH
Place of Publication:	PHILADELPHIA
ISSN:	1557-3265
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language SQUAMOUS-CELL CARCINOMA; DEFINITIVE CHEMORADIATION; DENDRITIC CELLS; NECK-CANCER; HEAD; CHEMOTHERAPY; RADIOTHERAPY; LYMPHOCYTES; LANDSCAPE; MARKERS Multiple languages Oncology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/60155