CD8, TIM3 Serve as Useful Prognostic Biomarkers for HCC

By Emily Menendez - Last Updated: March 19, 2025

CD8+ T cells play an important role in the anticancer immune response and are the preferred immune cells for targeting multiple forms of cancer, including hepatocellular carcinoma (HCC). T-cell immunoglobulin and mucin domain protein 3 (TIM3) work in tandem with CD8+ T cells by serving as key exhaustion markers. They are also associated with the suppression of antitumor immunity and tumor progression in HCC.

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In a study presented by Mitsuo Shimada, MD, PhD, at the 2024 American Society of Clinical Oncology Gastrointestinal Cancers Symposium, CD8 and TIM3 were investigated for their potential association with PD-1/PD-L1 expression and survival outcomes to determine their status as prognostic biomarkers for HCC.

Researchers used the Cancer Genome Atlas (TCGA; n=359) and Gene Expression Omnibus (GEO; n=115) database repositories to gather clinical and transcriptomic data from 474 patients with HCC. Using the tertiles of gene expression, each gene was divided into low- and high-expression groups.

In the TCGA dataset, patients with high CD8 and low TIM3 expression were found to have better overall survival (OS) rates (P=.021 and P=.025, respectively), while PD-1/PD-L1 were not associated with OS (P=.306 and P=.318, respectively). Patients with high CD8 and low TIM3 expression were also validated in the GEO dataset (P=.014 and P=.009, respectively).

Compared with HCC patients overall, those with high CD8 and low TIM3 expression had an improved OS (P=.008). In patients with high CD8 expression, low TIM3 expression was also associated with better OS (P=.009), but PD-1/PD-L1 were not associated with OS (P=.491 and P=.772, respectively).

A multivariate analysis showed that patients with nonexhausted CD8+ T cells had significantly superior survival outcomes (hazard ratio, 2.80; 95% CI, 1.27-6.19; P=.01).

In patients with HCC, high CD8 expression and low TIM3 expression were linked to better OS than PD-1/PD-L1, showing that CD8 and TIM3 can serve as useful biomarkers for predicting prognosis. Restoring exhausted T cells by suppressing TIM3 can be an effective tactic for the treatment of HCC.

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