肿瘤内在核 β-catenin 与头颈部鳞状细胞癌的免疫忽视表型及较差预后相关

Activation of WNT/ -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 -catenin signaling and TME inflammation in head and neck squamous cell carcinomas (HNSCCs). Membrane and nuclear -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 -catenin levels decreased in carcinomas compared to the normal epithelium.

Positive nuclear -catenin was detected in 50 tumors (14. 3%) and was significantly associated with a low CD8+ TIL density (168 cells/mm 2 versus 293 cells/mm 2 in nuclear- -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 -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 -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.