Pancreatic Cancers with High Grade Tumor Budding Exhibit Hallmarks of Diminished Anti-Tumor Immunity.

Sadozai, Hassan; Acharjee, Animesh; Gruber, Thomas; Gloor, Beat; Karamitopoulou, Eva (2021). Pancreatic Cancers with High Grade Tumor Budding Exhibit Hallmarks of Diminished Anti-Tumor Immunity. Cancers, 13(5) MDPI AG 10.3390/cancers13051090

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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 leukocytes 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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Service Sector > Institute of Pathology
04 Faculty of Medicine > Department of Gastro-intestinal, Liver and Lung Disorders (DMLL) > Clinic of Visceral Surgery and Medicine > Visceral Surgery
04 Faculty of Medicine > Service Sector > Institute of Pathology > Immunopathology
04 Faculty of Medicine > Service Sector > Institute of Pathology > Tumour Pathology

UniBE Contributor:

Gloor, Beat and Karamitopoulou Diamantis, Evanthia

Subjects:

500 Science > 570 Life sciences; biology
600 Technology > 610 Medicine & health

ISSN:

2072-6694

Publisher:

MDPI AG

Language:

English

Submitter:

Rahel Fuhrer

Date Deposited:

24 Sep 2021 08:37

Last Modified:

24 Sep 2021 08:37

Publisher DOI:

10.3390/cancers13051090

PubMed ID:

33806316

Uncontrolled Keywords:

M1/M2 macrophages T cell-enriched T lymphocytes gene signature pancreatic ductal adenocarcinoma (PDAC) tumor budding

BORIS DOI:

10.48350/159325

URI:

https://boris.unibe.ch/id/eprint/159325

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