Programmed Death Ligand-1 (PD-L1) Is an Independent Negative Prognosticator in Western-World Gallbladder Cancer

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.

Novel immune scoring dynamic nomograms based on B7-H3, B7-H4, and HHLA2: Potential prediction in survival and immunotherapeutic efficacy for gallbladder cancer

“…Immune checkpoint blockade of the PD-1/PD-L1 axis has been proven to be effective in many kinds of tumors ( 8 ). However, a low proportion of PD-L1 overexpression (only 12% to 23%) ( 9 – 12 ), MMR protein deficiency (only 1.3%) ( 14 ), and MSI (less than 2%) ( 4 ) were identified in GBC tissue, all of which indicated that a significant proportion of GBC patients could not benefit from the immunotherapeutic strategies focusing on the PD-L1/PD-1 axis. Further exploring the B7-third group is necessary.…”

Camrelizumab Combined With Gemcitabine and Albumin-Bound Paclitaxel for Neoadjuvant Therapy in the Treatment of Progressive Gallbladder Cancer: A Case Report

“…Recent studies have found that the peripheral blood levels of circulating hematologic and serum cytokines and MAGE1 might serve as potential cancer biomarkers (17)(18)(19). Albrecht et al (20) reported that there is limited evidence on the efficacy of PD-1 inhibitors combined with other chemotherapeutic agents for GBC. The authors also reported that PD-L1 is upregulated in tumors and immune cells in a subpopulation of advanced Western GBC, providing evidence that the TIGIT/CD155 axis is a novel immune checkpoint for complement therapy for GBC.…”

Expression of HER2 and Mismatch Repair Proteins in Surgically Resected Gallbladder Adenocarcinoma

“…We evaluated a relatively large number of surgically resected GBCs and observed only a small subset of MSI-high GBC cases (1.3%), with no obvious clinicopathologic association. Several previous papers evaluated PD-1 expression in prognostic aspect of gallbladder cancers (46)(47)(48)(49)(50)(51), and one of the study reported association of MSI-H and PD-L1 expression (49). For precise evaluation of tumor infiltrating lymphocytes (TILs) and PD-L1 expression, TIL and PD-L1 expression should be evaluated mainly at the tumor-normal interphase, whole-section slides are required.…”