Prognostic Value of Immune Environment Analysis in Small Bowel Adenocarcinomas with Verified Mutational Landscape and Predisposing Conditions
Wirta, E.-V., Szeto, S., Hänninen, U., Ahtiainen, M., Böhm, J., Mecklin, J.-P., Aaltonen, L. A., & Seppälä, T. T. (2020). Prognostic Value of Immune Environment Analysis in Small Bowel Adenocarcinomas with Verified Mutational Landscape and Predisposing Conditions. Cancers, 12(8), Article 2018. https://doi.org/10.3390/cancers12082018
© 2020 the Authors
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. ...
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Additional information about fundingT.T.S. was supported by research grants from the Emil Aaltonen Foundation, Finnish Cancer Foundation, Sigrid Juselius Foundation, and Instrumentarium Science Foundation. J.P.M. was supported by the Finnish Cancer Foundation, Jane and Aatos Erkko Foundation, and State Research Fund. U.A.H. and L.A.A. were supported by the Academy of Finland (Centre of Excellence in Tumor Genetics Research 2018–2023 (312041)), Finnish Cancer Society, Sigrid Juselius Foundation, Jane and Aatos Erkko Foundation, and iCAN Digital Precision Cancer Medicine Flagship. ...
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