Elevated expression of B7 homolog 4 is associated with disease progression in upper urinary tract urothelial carcinoma.
Cancer Immunol Immunother
; 71(3): 565-578, 2022 Mar.
Article
en En
| MEDLINE
| ID: mdl-34275008
ABSTRACT
BACKGROUND:
B7 homolog 4 (B7-H4) is a negative regulator of immune responses, but its immunoregulatory role in the tumor microenvironment of upper urinary tract urothelial carcinoma (UTUC) remains unclear.METHODS:
We measured the immunohistochemical expression of B7-H4, CD8 and T cell intracellular antigen 1 (TIA-1), a marker of activated CD8, in 133 patients with UTUC who underwent nephroureterectomy. We also studied the relationship between B7-H4, CD8 and TIA-1 expression and clinicopathological characteristics.RESULTS:
B7-H4 was mainly expressed on the surface in tumor cells, while CD8 and TIA-1 were often expressed in tumor-infiltrating lymphocytes. Elevated expression of B7-H4 in tumor cells was associated with a poorer histological grade, higher pT stage, regional lymph node metastasis, lymphovascular invasion, poorer response of recurrent metastatic lesions to systemic chemotherapy and shorter overall survival. Expression of CD-8 or TIA-1 alone did not correlate directly with clinicopathological characteristics, but among the patients with higher B7-H4 expression in the primary tumors, those with higher CD8 or TIA-1 expression had a better response to systemic chemotherapy, and longer survival, than these with lower CD8 or TIA-1 expression. Cox multivariate regression analysis revealed that higher expression of B7-H4 was associated with shorter overall survival.CONCLUSIONS:
These findings suggest that B7-H4 expression in the tumor microenvironment influences the progression of UTUC through cancer immunity and metabolic activity. Tumor cell-associated B7-H4 might be a potential target for cancer immunotherapies.Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Biomarcadores de Tumor
/
Regulación Neoplásica de la Expresión Génica
/
Neoplasias Urológicas
/
Inhibidor 1 de la Activación de Células T con Dominio V-Set
Tipo de estudio:
Prognostic_studies
/
Risk_factors_studies
Límite:
Female
/
Humans
/
Male
Idioma:
En
Revista:
Cancer Immunol Immunother
Asunto de la revista:
ALERGIA E IMUNOLOGIA
/
NEOPLASIAS
/
TERAPEUTICA
Año:
2022
Tipo del documento:
Article
País de afiliación:
Japón