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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
- 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.
- Subjects :
- Squamous Cell Carcinoma of Head and Neck
Organic Chemistry
General Medicine
CD8-Positive T-Lymphocytes
B7-H1 Antigen
Catalysis
Computer Science Applications
Inorganic Chemistry
Lymphocytes, Tumor-Infiltrating
Phenotype
Head and Neck Neoplasms
Tumor Microenvironment
Humans
head and neck
squamous cell carcinoma
β-catenin
tumor infiltrating lymphocytes
PD-L1
Physical and Theoretical Chemistry
Molecular Biology
beta Catenin
Spectroscopy
Subjects
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