Pancreatic cancers with high grade tumor budding exhibit hallmarks of diminished anti-tumor immunity

Hassan Sadozai, Animesh Acharjee, Thomas Gruber, Beat Gloor, Eva Karamitopoulou

    Research output: Contribution to journalArticlepeer-review

    4 Citations (Scopus)

    Abstract

    Tumor budding is associated with epithelial-mesenchymal transition and diminished survival in a number of cancer types including pancreatic ductal adenocarcinoma (PDAC). In this study, we dissect the immune landscapes of patients with high grade versus low grade tumor budding to determine the features associated with immune escape and disease progression in pancreatic cancer. We performed immunohistochemistry-based quantification of tumor-infiltrating leuko-cytes and tumor bud assessment in a cohort of n = 111 PDAC patients in a tissue microarray (TMA) format. Patients were divided based on the ITBCC categories of tumor budding as Low Grade (LG: categories 1 and 2) and High Grade (HG: category 3). Tumor budding numbers and tumor budding grade demonstrated a significant association with diminished overall survival (OS). HG cases exhibit notably reduced densities of stromal (S) and intratumoral (IT) T cells. HG cases also display lower M1 macrophages (S) and increased M2 macrophages (IT). These findings were validated using gene expression data from TCGA. A published tumor budding gene signature demonstrated a significant association with diminished survival in PDAC patients in TCGA. Immune-related gene expression revealed an immunosuppressive TME in PDAC cases with high expression of the budding signature. Our findings highlight a number of immune features that permit an improved understanding of disease progression and EMT in pancreatic cancer.

    Original languageEnglish
    Article number1090
    Number of pages18
    JournalCancers
    Volume13
    Issue number5
    DOIs
    Publication statusPublished - 4 Mar 2021

    Bibliographical note

    Funding Information:
    E.K. was supported for this project by the Foundation for Clinical-Experimental Tumor-Research. The funders had no involvement in the study design; in the collection, analysis and in-terpretation of the data; in the writing of the report; and in the decision to submit the paper for publication. A.A. was supported by National Institute for Health Research (NIHR) Surgical Reconstruction and Microbiology Research Centre (SRMRC), Birmingham, UK. The views expressed in this publication are those of the authors and not necessarily those of the NHS, the National Institute for Health Research, the Medical Research Council or the Department of Health, UK.

    Funding Information:
    Funding: E.K. was supported for this project by the Foundation for Clinical-Experimental Tumor-Research. The funders had no involvement in the study design; in the collection, analysis and interpretation of the data; in the writing of the report; and in the decision to submit the paper for publication. A.A. was supported by National Institute for Health Research (NIHR) Surgical Reconstruction and Microbiology Research Centre (SRMRC), Birmingham, UK. The views expressed in this publication are those of the authors and not necessarily those of the NHS, the National Institute for Health Research, the Medical Research Council or the Department of Health, UK.

    Publisher Copyright:
    © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

    Copyright:
    Copyright 2021 Elsevier B.V., All rights reserved.

    Keywords

    • Gene signature
    • M1/M2 macrophages
    • Pancreatic ductal adenocarcinoma (PDAC)
    • T cell-enriched
    • T lympho-cytes
    • Tumor budding

    ASJC Scopus subject areas

    • Oncology
    • Cancer Research

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