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Tumor-Intrinsic Nuclear β-Catenin Associates with an Immune Ignorance Phenotype and a Poorer Prognosis in Head and Neck Squamous Cell Carcinomas

Authors :
Mario Sánchez-Canteli
Luis Juesas
Irati Garmendia
María Otero-Rosales
Alfonso Calvo
Monica Alvarez-Fernández
Aurora Astudillo
Luis M. Montuenga
Juana M. García-Pedrero
Juan P. Rodrigo
Source :
International Journal of Molecular Sciences; Volume 23; Issue 19; Pages: 11559, Scopus
Publication Year :
2022
Publisher :
MDPI AG, 2022.

Abstract

Activation of WNT/β-catenin signaling has been associated with a non-T-cell-inflamed tumor microenvironment (TME) in several cancers. The aim of this work was to investigate the relationship between β-catenin signaling and TME inflammation in head and neck squamous cell carcinomas (HNSCCs). Membrane and nuclear β-catenin expression, PD-L1 expression, and CD8+ tumor-infiltrating lymphocyte (TIL) density were jointly evaluated by immunohistochemistry in a series of 372 HPV-negative HNSCCs. Membrane β-catenin levels decreased in carcinomas compared to the normal epithelium. Positive nuclear β-catenin was detected in 50 tumors (14.3%) and was significantly associated with a low CD8+ TIL density (168 cells/mm2 versus 293 cells/mm2 in nuclear-β-catenin-negative cases; p = 0.01) and a tendency for a lower expression of PD-L1, resulting in association with a noninflamed TME (i.e., type II, immunological ignorance). Multivariate Cox analysis further demonstrated that low infiltration by CD8+ TILs (HR = 1.6, 95% CI = 1.19–2.14, p = 0.002) and nuclear β-catenin expression (HR = 1.47, 95% CI = 1.01–2.16, p = 0.04) were both independently associated with a poorer disease-specific survival. In conclusion, tumor-intrinsic nuclear β-catenin activation is associated with a non-inflamed TME phenotype and a poorer prognosis, thereby suggesting a possible implication as an immune exclusion mechanism for a subset of HNSCC patients.

Details

ISSN :
14220067
Volume :
23
Database :
OpenAIRE
Journal :
International Journal of Molecular Sciences
Accession number :
edsair.doi.dedup.....a972b31fa9941ff145066ac124d05c51
Full Text :
https://doi.org/10.3390/ijms231911559