B7-H3 expression is associated with high PD-L1 expression in clear cell renal cell carcinoma and predicts poor prognosis

Diagn Pathol. 2023 Mar 9;18(1):36. doi: 10.1186/s13000-023-01320-0.

Abstract

Background: Clear cell Renal cell carcinoma (ccRCC) is an immunogenic tumor. B7 family members, such as CTLA-4, PD-1, and PD-L1, are the main components of immune checkpoints that regulate various immune responses. Specifically, B7-H3 regulates T cell-mediated immune responses against cancer. This study aimed to analyze the association between B7-H3 and CTLA-4 expression and the prognostic factors of ccRCC to provide a basis for their potential use as predictive factors and in immunotherapy.

Methods: Formalin-fixed paraffin-embedded specimens were obtained from 244 ccRCC patients, and B7-H3, CTLA-4, and PD-L1 expressions were evaluated using immunohistochemical staining.

Results: B7-H3 and CTLA-4 were positive in 73 (29.9%) and 57 (23.4%) of the 244 patients, respectively. B7-H3 expression was significantly associated with PD-L1 expression (P < 0.0001); however, CTLA-4 expression was not (P = 0.842). Kaplan-Meier analysis showed that positive B7-H3 expression was associated with poor progression-free survival (PFS) (P < 0.0001), whereas CTLA-4 expression was not (P = 0.457). Multivariate analysis revealed that B7-H3 was correlated with poor PFS (P = 0.031), whereas CTLA-4 was not (P = 0.173).

Conclusions: To the best of our knowledge, this study is the first to investigate B7-H3 and PD-L1 expression and survival in ccRCC. B7-H3 expression is an independent prognostic factor for ccRCC. Furthermore, multiple immune cell inhibitory targets, such as B7-H3 and PD-L1, can be used for therapeutic tumor regression in a clinical setting.

Keywords: B7-H3; Clear cell renal cell carcinoma; PD-L1; Prognosis.

MeSH terms

  • B7-H1 Antigen / metabolism
  • Biomarkers, Tumor / analysis
  • Carcinoma, Renal Cell* / pathology
  • Humans
  • Kaplan-Meier Estimate
  • Kidney Neoplasms* / pathology
  • Prognosis

Substances

  • B7-H1 Antigen
  • Biomarkers, Tumor
  • CD276 protein, human