Next Article in Journal
The Chicken Chorioallantoic Membrane Tumor Assay as a Relevant In Vivo Model to Study the Impact of Hypoxia on Tumor Progression and Metastasis
Next Article in Special Issue
KRAS Mutation Dictates the Cancer Immune Environment in Pancreatic Ductal Adenocarcinoma and Other Adenocarcinomas
Previous Article in Journal
The Role of Cancer Stem Cells in Colorectal Cancer: From the Basics to Novel Clinical Trials
Previous Article in Special Issue
Understanding and Targeting Natural Killer Cell-Cancer-Associated Fibroblast Interactions in Pancreatic Ductal Adenocarcinoma
 
 
Article

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

1
Center for Sport, Exercise and Life Sciences, Coventry University, Coventry CV1 5FB, UK
2
Institute of Cancer and Genomic Sciences, Centre for Computational Biology, College of Medical and Dental Sciences, University of Birmingham, Birmingham B15 2TT, UK
3
Institute of Translational Medicine, University Hospitals Birmingham NHS Foundation Trust, Birmingham B15 2TH, UK
4
NIHR Surgical Reconstruction and Microbiology Research Centre, University Hospital Birmingham, Birmingham B15 2WB, UK
5
Independent Scholar, NCIS—National Coalition of Independent Scholars, CH-3930 Visp, Switzerland
6
Department of Visceral Surgery, Insel University Hospital, University of Bern, CH-3010 Bern, Switzerland
7
Pancreatic Cancer Research Group, Institute of Pathology, University of Bern, Murtenstrasse 31, CH-3008 Bern, Switzerland
*
Author to whom correspondence should be addressed.
Academic Editor: Huey-Jen Lin
Cancers 2021, 13(5), 1090; https://doi.org/10.3390/cancers13051090
Received: 14 February 2021 / Revised: 26 February 2021 / Accepted: 28 February 2021 / Published: 4 March 2021
(This article belongs to the Special Issue Tumor Microenvironment of Pancreatic Cancer)
Pancreatic cancer, in its most common manifestation pancreatic ductal adenocarcinoma (PDAC), is a uniquely lethal disease with very limited treatment options and few prognostic biomarkers. Tumor budding is a proven independent, adverse prognostic factor in many tumor types including PDAC. Tumor buds can be detected histologically as single cancer cells or clusters of up to four cancer cells at the tumor invasive front. Tumor budding is biologically correlated to the induction of epithelial-mesenchymal transitions (EMT) and disease progression. In this study, we sought to investigate the immunological composition of tumors with high levels of tumor budding. We show that PDAC cases with a high grade of tumor budding display notably diminished anti-tumor immunity. These findings were further validated by gene expression analysis of PDAC cases from The Cancer Genome Atlas (TCGA). Our results provide insight on the immune escape mechanisms of tumor cells undergoing EMT. This offers the potential of designing novel treatments combining immunotherapies with EMT-targeted drugs.
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. View Full-Text
Keywords: pancreatic ductal adenocarcinoma (PDAC); tumor budding; gene signature; T lymphocytes; T cell-enriched; M1/M2 macrophages pancreatic ductal adenocarcinoma (PDAC); tumor budding; gene signature; T lymphocytes; T cell-enriched; M1/M2 macrophages
Show Figures

Figure 1

MDPI and ACS Style

Sadozai, H.; Acharjee, A.; Gruber, T.; Gloor, B.; Karamitopoulou, E. Pancreatic Cancers with High Grade Tumor Budding Exhibit Hallmarks of Diminished Anti-Tumor Immunity. Cancers 2021, 13, 1090. https://doi.org/10.3390/cancers13051090

AMA Style

Sadozai H, Acharjee A, Gruber T, Gloor B, Karamitopoulou E. Pancreatic Cancers with High Grade Tumor Budding Exhibit Hallmarks of Diminished Anti-Tumor Immunity. Cancers. 2021; 13(5):1090. https://doi.org/10.3390/cancers13051090

Chicago/Turabian Style

Sadozai, Hassan, Animesh Acharjee, Thomas Gruber, Beat Gloor, and Eva Karamitopoulou. 2021. "Pancreatic Cancers with High Grade Tumor Budding Exhibit Hallmarks of Diminished Anti-Tumor Immunity" Cancers 13, no. 5: 1090. https://doi.org/10.3390/cancers13051090

Find Other Styles
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop