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. 2025 May 1;48(4):147-158.
doi: 10.1097/CJI.0000000000000550. Epub 2025 Mar 4.

RBBP8 Is a Prognostic Biomarker Associated With Response to Immune Checkpoint Inhibitors in Advanced Gastric Cancer

Taiki Nakashima  1 , Ryu Matsumoto, Kiyonori Tanoue, Chieri Nakayama, Kazuki Sameshima, Yuto Hozaka, Takaaki Arigami, Daisuke Matsushita, Masataka Shimonosono, Yusuke Tsuruda, Ken Sasaki, Yuko Mataki, Takao Ohtsuka
Affiliations

RBBP8 Is a Prognostic Biomarker Associated With Response to Immune Checkpoint Inhibitors in Advanced Gastric Cancer

Taiki Nakashima et al. J Immunother. .

Abstract

The current biomarkers for immune checkpoint inhibitor (ICI) therapy have several limitations, and new ones are being explored. Retinoblastoma-binding protein 8 (RBBP8) is associated with tumor-infiltrating immune cells (TIIC) and immune checkpoint molecules. Therefore, RBBP8 may serve as a novel biomarker for ICI therapy. Thus, in this study, we investigated the relationship between RBBP8 expression and the tumor immune environment in 58 patients with pathologic T3-4 gastric cancer who underwent radical gastrectomy. Immunohistochemistry of primary tumor specimens was performed to evaluate RBBP8, TIIC, and programmed cell death ligand 1 expression. Kaplan-Meier survival and prognostic factor analyses were also performed using Cox proportional hazards regression models. Patients were divided into RBBP8 high (HG, n=29) and low (LG, n=29) expression groups, using the median RBBP8 expression as the cutoff. The LG had a significantly worse overall survival rate than the HG (log-rank test, P =0.029). Furthermore, the overall survival rate of patients in LG who were treated with ICI (n=7) was worse than that of those in HG (n=9; log-rank P =0.005). Multivariate analysis identified extensive lymph node metastasis and low RBBP8 expression as independent prognostic factors. The HG and LG showed no significant difference in the number of TIICs; however, there was a difference in the number ratios of CD4+/CD8+ ( P =0.012) and CD4+/CD3+ cells ( P <0.001). Therefore, RBBP8 expression in patients with advanced gastric cancer is a prognostic marker that affects the proportion of CD4+ T-cell infiltration and may also be a biomarker for predicting ICI treatment response.

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