Prognostic value of immune environment analysis in small bowel adenocarcinomas with verified mutational landscape and predisposing conditions

Erkki Ville Wirta, Säde Szeto, Ulrika Hänninen, Maarit Ahtiainen, Jan Böhm, Jukka Pekka Mecklin, Lauri A. Aaltonen, Toni T. Seppälä

    Research output: Contribution to journalArticleScientificpeer-review

    7 Citations (Scopus)

    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.

    Original languageEnglish
    Article number2018
    Number of pages19
    JournalCancers
    Volume12
    Issue number8
    DOIs
    Publication statusPublished - 2020
    Publication typeA1 Journal article-refereed

    Keywords

    • Adenocarcinoma
    • PD-1
    • PD-L1
    • Small bowel
    • Tumour infiltrating lymphocytes

    Publication forum classification

    • Publication forum level 1

    ASJC Scopus subject areas

    • Oncology
    • Cancer Research

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