SORA

Advancing, promoting and sharing knowledge of health through excellence in teaching, clinical practice and research into the prevention and treatment of illness

Effect of Gemcitabine based chemotherapy on the immunogenicity of pancreatic tumour cells and T-cells.

Smith, PL; Yogaratnam, Y; Samad, M; Kasow, S; Dalgleish, AG (2021) Effect of Gemcitabine based chemotherapy on the immunogenicity of pancreatic tumour cells and T-cells. Clin Transl Oncol, 23 (1). pp. 110-121. ISSN 1699-3055 https://doi.org/10.1007/s12094-020-02429-0
SGUL Authors: Dalgleish, Angus George Smith, Peter Lawrence

[img]
Preview
PDF Published Version
Available under License Creative Commons Attribution.

Download (5MB) | Preview

Abstract

PURPOSE: Chemotherapy for advanced pancreatic cancer has limited efficacy due to the difficultly of treating established tumours and the evolution of tumour resistance. Chemotherapies for pancreatic cancer are typically studied for their cytotoxic properties rather than for their ability to increase the immunogenicity of pancreatic tumour cells. In this study Gemcitabine in combination with immune modulatory chemotherapies Oxaliplatin, zoledronic acid and pomalidomide was studied to determine how combination therapy alters the immunogenicity of pancreatic tumour cell lines and subsequent T-cell responses. METHODS: Pancreatic tumour cell lines were stimulated with the chemotherapeutic agents and markers of immune recognition were assessed. The effect of chemotherapeutic agents on DC function was measured using uptake of CFSE-stained PANC-1 cells, changes in markers of maturation and their ability to activate CD8+ T-cells. The effect of chemotherapeutic agents on T-cell priming prior to activation using anti-CD3 and anti-CD28 antibodies was determined by measuring IFN-γ expression and Annexin V staining using flow cytometry. RESULTS: These agents demonstrate both additive and inhibitory properties on a range of markers of immunogenicity. Gemcitabine was notable for its ability to induce the upregulation of human leukocyte antigen and checkpoints on pancreatic tumour cell lines whilst inhibiting T-cell activation. Pomalidomide demonstrated immune modulatory properties on dendritic cells and T-cells, even in the presence of gemcitabine. DISCUSSION: These data highlight the complex interactions of different agents in the modulation of tumour immunogenicity and immune cell activation and emphasise the complexity in rationally designing chemo immunogenic combinations for use with immunotherapy.

Item Type: Article
Additional Information: Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
Keywords: Chemotherapy, Gemcitabine, Immunotherapy, Pancreatic cancer, 1111 Nutrition and Dietetics, Oncology & Carcinogenesis
SGUL Research Institute / Research Centre: Academic Structure > Infection and Immunity Research Institute (INII)
Journal or Publication Title: Clin Transl Oncol
ISSN: 1699-3055
Language: eng
Dates:
DateEvent
January 2021Published
13 July 2020Published Online
12 May 2020Accepted
Publisher License: Creative Commons: Attribution 4.0
PubMed ID: 32661823
Go to PubMed abstract
URI: https://openaccess.sgul.ac.uk/id/eprint/112181
Publisher's version: https://doi.org/10.1007/s12094-020-02429-0

Actions (login required)

Edit Item Edit Item