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Programmed Death Ligand-1 (PD-L1) Is an Independent Negative Prognosticator in Western-World Gallbladder Cancer
Thomas Albrecht1,2, Fritz Brinkmann1,2, Michael Albrecht3
1Institute of Pathology, Heidelberg University Hospital, 69120 Heidelberg, Germany.
Abstract:
Inhibition of the programmed cell death protein-1/ligand-1 (PD-1/PD-L1) axis has opened a new era in the treatment of solid cancers. However, there is no data on the expression and relevance of PD-L1 in Western gallbladder cancer (GBC). We assessed PD-L1 immunohistochemically in 131 GBC patients as Tumor Proportion Score (TPS), Immune Cell Score (IC) and Combined Positivity Score (CPS). Tumor cells expressed PD-L1 in a subset of 14.7% GBC patients at a TPS cut-off of 1%. Higher PD-L1 levels above 10% and 25% TPS were reached in 4.7% and 3.1% of GBC cases, respectively. At a 10% cut-off, TPS was associated with distinct histomorphological subtypes and correlated with poor tumor differentiation. Survival analysis revealed a TPS above 10% to be a highly significant and independent negative prognosticator in GBC. PD-L1 expression was associated with increased CD4+, CD8+ and PD-1+ immune cell densities. In 14.8% of the cases, scattered immune cells expressed T-cell immunoreceptor with Ig and ITIM domains (TIGIT), which was correlated to tumoral expression of its ligand CD155. We here show that a high PD-L1 expression confers a negative prognostic value in Western-world GBC and highlight the TIGIT/CD155 immune checkpoint as a potential new target for GBC immunotherapy.
Insights
High programmed cell death protein-1 ligand-1 (PD-L1) expression indicates a poor prognosis in Western gallbladder cancer (GBC). This finding highlights PD-L1 as a negative prognosticator and suggests targeting the TIGIT/CD155 pathway for GBC immunotherapy.
Area of Science:
- Oncology
- Immunology
- Cancer Research
Background:
- The programmed cell death protein-1/ligand-1 (PD-1/PD-L1) axis is a key target in cancer immunotherapy.
- Data on PD-L1 expression and its clinical relevance in Western gallbladder cancer (GBC) is lacking.
Purpose of the Study:
- To investigate the expression and prognostic significance of PD-L1 in Western GBC.
- To explore potential new immunotherapy targets in GBC.
Main Methods:
- PD-L1 expression was assessed immunohistochemically in 131 GBC patients using Tumor Proportion Score (TPS), Immune Cell Score (IC), and Combined Positivity Score (CPS).
- Statistical analyses were performed to correlate PD-L1 expression with clinicopathological features and patient survival.
- Immune cell infiltration and TIGIT/CD155 expression were also evaluated.
Main Results:
- PD-L1 expression (TPS ≥ 1%) was observed in 14.7% of GBC cases.
- Higher PD-L1 levels (TPS > 10%) were associated with poor tumor differentiation and were a significant independent negative prognosticator.
- PD-L1 expression correlated with increased CD4+, CD8+, and PD-1+ immune cell densities.
- T-cell immunoreceptor with Ig and ITIM domains (TIGIT) expression was found in 14.8% of cases, correlated with CD155.
Conclusions:
- High PD-L1 expression is a negative prognostic factor in Western GBC.
- The TIGIT/CD155 immune checkpoint represents a potential novel therapeutic target for GBC immunotherapy.
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