Clinical relevance of <scp>PD</scp>‐L1 expression in gallbladder cancer: a potential target for therapy

<jats:sec><jats:title>Aims</jats:title><jats:p>Programmed death‐ligand 1 (<jats:styled-content style="fixed-case">PD</jats:styled-content>‐L1), a potential target for immune checkpoint inhibitors in various solid neoplasms, has been studied in very few cases of Gall Bladder Carcinoma (<jats:styled-content style="fixed-case">GBC</jats:styled-content>). The current study aimed to evaluate <jats:styled-content style="fixed-case">PD</jats:styled-content>‐L1 expression at primary and metastatic sites of <jats:styled-content style="fixed-case">GBC</jats:styled-content>, and its associations with standard prognostic clinicopathological parameters, as well as with overall survival.</jats:p></jats:sec><jats:sec><jats:title>Methods and results</jats:title><jats:p>One hundred and seventy‐four cases of <jats:styled-content style="fixed-case">GBC</jats:styled-content> were evaluated for <jats:styled-content style="fixed-case">PD</jats:styled-content>‐L1 expression by the use of the <jats:styled-content style="fixed-case">SP</jats:styled-content>263 clone in tissue microarrays. Clinicopathological characteristics and survival data were correlated with <jats:styled-content style="fixed-case">PD</jats:styled-content>‐L1 expression analysed at different cut‐offs of ≥1%, ≥10% and ≥50% in tumour cells and tumour‐infiltrating lymphocytes (<jats:styled-content style="fixed-case">TIL</jats:styled-content>s). The mean age of patients was 49.9 years, and the male/female ratio was 1:2.9. Of the cases, 73.6% presented with stage 3/4 disease. Tumour cells expressed <jats:styled-content style="fixed-case">PD</jats:styled-content>‐L1 in 23.0% of cases, and <jats:styled-content style="fixed-case">TIL</jats:styled-content>s expressed <jats:styled-content style="fixed-case">PD</jats:styled-content>‐L1 in 24.1% of cases. At a cut‐off of 10%, 14.9% of cases expressed <jats:styled-content style="fixed-case">PD</jats:styled-content>‐L1, and at a cut‐off of 50%, 7.5% of cases expressed <jats:styled-content style="fixed-case">PD</jats:styled-content>‐L1. Significant associations were seen between tumour proportion score and histological type (<jats:italic>P</jats:italic> = 0.004), histological grade (<jats:italic>P</jats:italic> = 0.004), nuclear grade (<jats:italic>P</jats:italic> = 0.008), nodal metastasis (<jats:italic>P</jats:italic> = 0.051), higher stage (<jats:italic>P</jats:italic> = 0.058), and <jats:styled-content style="fixed-case">TIL</jats:styled-content>s (<jats:italic>P</jats:italic> < 0.001). Tumour size, growth pattern, the presence of necrosis and lymphovascular emboli showed no significant associations with <jats:styled-content style="fixed-case">PD</jats:styled-content>‐L1 in tumour cells or <jats:styled-content style="fixed-case">TIL</jats:styled-content>s. In synchronous paired samples from primary and metastatic lymph nodes, discordantly higher <jats:styled-content style="fixed-case">PD</jats:styled-content>‐L1 expression was evident in lymph nodes. Overall survival was not associated with <jats:styled-content style="fixed-case">PD</jats:styled-content>‐L1 expression (<jats:italic>P</jats:italic> = 0.546).</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p><jats:styled-content style="fixed-case">PD</jats:styled-content>‐L1 does not appear to be a prognostic marker or influence survival in <jats:styled-content style="fixed-case">GBC</jats:styled-content> patients. However, <jats:styled-content style="fixed-case">PD</jats:styled-content>‐L1 expression occurs in one of four <jats:styled-content style="fixed-case">GBC</jats:styled-content>s, supporting the future possibility of immune‐modulation therapy to improve the dismal overall survival.</jats:p></jats:sec>