Comparative immune profiling of pancreatic ductal adenocarcinoma progression among South African patients

Theodor Bilharz Research Institute

Bibliographic Information

Authors: Elebo N.; Abdel-Shafy E.A.; Omoshoro-Jones J.A.O.; Nsingwane Z.; Hussein A.A.A.; Smith M.; Candy G.; Cacciatore S.; Fru P.; Nweke E.E.

Journal: BMC Cancer

Publisher: BioMed Central Ltd

Publication Date: 7 July 2024

Volume / Issue: Volume 24 / Issue 1

Article No.: 809

ISSN: 14712407

DOI: 10.1186/s12885-024-12595-x

Scopus: View on Scopus

PubMed: 38973003

Document Type: Article

Access: All Open Access; Gold Open Access; Green Open Access

Authors and Affiliations

Elebo N., Department of Surgery, Faculty of Health Sciences, University of Witwatersrand, Johannesburg, 2193, South Africa, Bioinformatics Unit, International Centre for Genetic Engineering and Biotechnology, Observatory, Cape Town, 7925, South Africa; Abdel-Shafy E.A., Bioinformatics Unit, International Centre for Genetic Engineering and Biotechnology, Observatory, Cape Town, 7925, South Africa, National Research Centre, Cairo, Egypt; Omoshoro-Jones J.A.O., Department of Surgery, Faculty of Health Sciences, University of Witwatersrand, Johannesburg, 2193, South Africa, Hepatopancreatobiliary Unit, Department of Surgery, Chris Hani-Baragwanath Academic Hospital, Soweto Johannesburg, South Africa; Nsingwane Z., Department of Surgery, Faculty of Health Sciences, University of Witwatersrand, Johannesburg, 2193, South Africa; Hussein A.A.A., Bioinformatics Unit, International Centre for Genetic Engineering and Biotechnology, Observatory, Cape Town, 7925, South Africa, Theodore Bilharz Research Institute, Giza, Egypt; Smith M., Department of Surgery, Faculty of Health Sciences, University of Witwatersrand, Johannesburg, 2193, South Africa, Hepatopancreatobiliary Unit, Department of Surgery, Chris Hani-Baragwanath Academic Hospital, Soweto Johannesburg, South Africa; Candy G., Department of Surgery, Faculty of Health Sciences, University of Witwatersrand, Johannesburg, 2193, South Africa; Cacciatore S., Bioinformatics Unit, International Centre for Genetic Engineering and Biotechnology, Observatory, Cape Town, 7925, South Africa; Fru P., Department of Surgery, Faculty of Health Sciences, University of Witwatersrand, Johannesburg, 2193, South Africa; Nweke E.E., Department of Surgery, Faculty of Health Sciences, University of Witwatersrand, Johannesburg, 2193, South Africa, Department of Life and Consumer Sciences, College of Agriculture and Environmental Sciences, University of South Africa, Florida, Roodepoort, South Africa

Abstract

Background: Pancreatic Ductal Adenocarcinoma (PDAC) is an aggressive cancer characterized by an immunosuppressive microenvironment. Patients from specific ethnicities and population groups have poorer prognoses than others. Therefore, a better understanding of the immune landscape in such groups is necessary for disease elucidation, predicting patient outcomes and therapeutic targeting. This study investigated the expression of circulating key immune cell markers in South African PDAC patients of African ancestry. Methods: Blood samples were obtained from a total of 6 healthy volunteers (HC), 6 Chronic Pancreatitis (CP) and 34 PDAC patients consisting of 22 resectable (RPC), 8 locally advanced (LAPC) and 4 metastatic (MPC). Real-time Quantitative Polymerase Chain reactions (RT-qPCR), Metabolomics, Enzyme-Linked Immunosorbent Assay (ELISA), Reactive Oxygen Species (ROS), and Immunophenotyping assays were conducted. Statistical analysis was conducted in R (v 4.3.2). Additional analysis of single-cell RNA data from 20 patients (16 PDAC and 4 controls) was conducted to interrogate the distribution of T-cell and Natural Killer cell populations. Results: Granulocyte and neutrophil levels were significantly elevated while lymphocytes decreased with PDAC severity. The total percentages of CD3 T-cell subpopulations (helper and double negative T-cells) decreased when compared to HC. Although both NK (p = 0.014) and NKT (p < 0.001) cell levels increased as the disease progressed, their subsets: NK CD56dimCD16− (p = 0.024) and NKTs CD56+ (p = 0.008) cell levels reduced significantly. Of note is the negative association of NK CD56dimCD16− (p < 0.001) cell levels with survival time. The gene expression analyses showed no statistically significant correlation when comparing the PDAC groups with the controls. The inflammatory status of PDAC was assessed by ROS levels of serum which were elevated in CP (p = 0.025), (RPC (p = 0.003) and LAPC (p = 0.008)) while no significant change was observed in MPC, compared to the HC group. ROS was shown to be positively correlated with GlycA (R = 0.45, p = 0.0096). Single-cell analyses showed a significant difference in the ratio of NKT cells per total cell counts in LAPC (p < 0.001) and MPC (p < 0.001) groups compared with HC, confirming observations in our sample group. Conclusion: The expression of these immune cell markers observed in this pilot study provides insight into their potential roles in tumour progression in the patient group and suggests their potential utility in the development of immunotherapeutic strategies. © The Author(s) 2024.

Keywords

CD4; CD8; Immune cells; Immunosuppression; Pancreatic ductal adenocarcinoma; PDAC; Adult; Aged; Biomarkers, Tumor; Carcinoma, Pancreatic Ductal; Disease Progression; Female; Humans; Immunophenotyping; Killer Cells, Natural; Male; Middle Aged; Pancreatic Neoplasms; Pancreatitis, Chronic; Reactive Oxygen Species; South Africa; CD16 antigen; CD4 antigen; CD56 antigen; CD57 antigen; CD8 antigen; interleukin 10; reactive oxygen metabolite; tumor marker; Article; cancer growth; cancer survival; CD3+ T lymphocyte; CD4 lymphocyte count; CD4+ T lymphocyte; CD8+ T lymphocyte; cholangitis; chronic pancreatitis; controlled study; cytotoxicity; enzyme linked immunosorbent assay; flow cytometry; fluorescence activated cell sorting; gene expression; human; hypertension; immune response; immunocompetent cell; immunometabolism; immunosuppressive treatment; major clinical study; metabolomics; natural killer cell; natural killer T cell; neutrophil; neutrophil lymphocyte ratio; non insulin dependent diabetes mellitus; normal human; nuclear magnetic resonance; overall survival; oxidative stress; pancreas cancer; pancreatic ductal carcinoma; peripheral blood mononuclear cell; protein expression; real time polymerase chain reaction; regulatory T lymphocyte; single cell RNA seq; survival time; T lymphocyte; tumor growth; comparative study; disease exacerbation; genetics; immunology; metabolism; pancreas tumor; pathology

Citation Information

Scopus Citations: 5

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