Abstract
Background: Small bowel adenocarcinoma (SBA) is a rare yet insidious cancer with poor survival. The abundance of tumour-infiltrating lymphocytes is associated with improved survival, but the role of the programmed death-1/programmed death ligand-1 (PD-1/PD-L1) pathway in tumour escape is controversial. We evaluated immune cell infiltration, PD1/PD-L1 expression and their prognostic value in a series of SBAs with previously verified predisposing conditions and exome-wide somatic mutation characterization. Methods: Formalin-fixed paraffin-embedded tissue sections stained for CD3, CD8, PD-L1 and PD-1 were analysed from 94 SBAs. An immune cell score (ICS) was formed from the amount of the CD3 and CD8 positive lymphocytes from the tumour centre and invasive margin. The PD-L1 and PD-1 positive immune cells (ICs) and ICS were combined into a variable called Immunoprofile. Results: High ICS, PD-L1IC and PD-1, individually and combined as Immunoprofile, were prognostic for better patient outcome. Sixty-five (69%) SBAs expressed ≥1% positive PD-L1IC. A high tumour mutation burden was common (19%) and associated with immune markers. Immunoprofile, adjusted for TNM stage, mismatch repair status, tumour location, sex and age were independent prognostic markers for disease-specific and overall survival. Conclusions: Analysing tumoral immune contexture provides prognostic information in SBA. Combining ICS, PD-1 and PD-L1IC as Immunoprofile enhanced the prognostic performance.
Highlights
The small bowel is perhaps the most powerful organ in the human body in terms of regulating the immune system
We found that the only notable correlation between different mutation patterns and immune parameters was the correlation of mutational signature 17 with PD-L1IC, and, with
We found that a high portion of Small bowel adenocarcinoma (SBA) express ≥1% of programmed death ligand-1 (PD-L1) in immune cells within the tumour environment, and a high tumour mutational burden (TMB) is relatively common, mainly seen in microsatellite instability (MSI) tumours
Summary
The small bowel is perhaps the most powerful organ in the human body in terms of regulating the immune system. This may explain why small bowel cancers are rare, comprising only approximately 3%. Adenocarcinomas account for approximately 40% of all malignant small bowel tumours and are most commonly found. Known risk factors for SBA include Crohn’s disease and coeliac disease, which both cause chronic inflammation of the small bowel [5]. Small bowel adenocarcinoma (SBA) is a rare yet insidious cancer with poor survival. Methods: Formalin-fixed paraffin-embedded tissue sections stained for CD3, CD8, PD-L1 and PD-1 were analysed from 94 SBAs. An immune cell score (ICS) was formed from the amount of the CD3 and CD8 positive lymphocytes from the tumour centre and invasive margin.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
