PD-1, PD-L1 and PD-L2 Expression in Well-Differentiated Small Bowel Gastrointestinal Neuroendocrine Tumours (Wd SB-NETs)

Introduction: Treatment options for patients with advanced Wd SB-NETs are limited. Aim(s): We describe immune cell infiltration in this disease group. Materials and methods: Patients diagnosed with Wd (WHO grade 1-2) SB-NETs, who had provided informed consent for analysis of archival tissue, were eligible. Programmed death-ligand 1 (PD-L1), PD-L2, PD-1 and tumour infiltrating lymphocytes (TILs) were analysed by immunohistochemistry (IHC); PD-L1, PD1 and PD-L2 were also assessed with reverse transcription polymerase chain reaction (RT-PCR). Results: Of 109 patients screened, 62 were eligible: 54.8% male, median age 64 years; stage II 4.8%, III 40.3% and IV 54.8%; 41.9% were “functioning”. In total, 70 and 63 samples were eligible for IHC and RT-PCR analysis, respectively. Analysed samples were grade (G)1 (67.1%) or G2 (32.86%) NETs; median Ki-67 2%; 67.1% primary SB, 32.86% metastatic sites. There was PD-L1 expression within tumour cells and TILs in 12.8% and 24.3% of samples, respectively. PD1 was present in TILs in 22.8% of samples. No IHC expression of PD-L2 was identified. The majority of samples showed significant presence of CD4 (focal 42.86%; moderate 2.86%) and CD8 (focal 92.86%; moderate 4.29%) TILs. IHC findings were confirmed with RT-PCR which demonstrated higher expression of PD-L1 (p-value 0.007) and PD1 (p-value 0.001) in samples with positive- compared to negative-IHC, respectively. Conclusion: Due to the observed expression of TILs, the role of immune check-point inhibitors may be explored in this setting.