期刊
CANCER IMMUNOLOGY IMMUNOTHERAPY
卷 71, 期 3, 页码 565-578出版社
SPRINGER
DOI: 10.1007/s00262-021-03011-5
关键词
B7 homolog 4 (B7-H4); CD8; T cell intracellular antigen 1 (TIA-1); Programmed cell death 1 ligand 1 (PD-L1); Tumor-infiltrating lymphocyte (TIL); Upper tract urothelial carcinoma (UTUC)
资金
- Japanese Science Progress Society KAKENHI [20K09546]
- Grants-in-Aid for Scientific Research [20K09546] Funding Source: KAKEN
The study found that in UTUC patients, the expression of B7-H4 in the tumor microenvironment is related to tumor progression, response to chemotherapy, and overall survival. The expression of CD8 and TIA-1 also influences patient response to chemotherapy and survival.
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.
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