Abstract
Gemcitabine has been used as a chemotherapeutic to treat solid cancers for more than 20 years. Whilst its use as chemotherapy has been declining due to the development of more potent chemotherapeutic combinations further studies of gemcitabine have identified varied immune modulatory effects on both tumour cells and leukocyte subsets
Highlights
Gemcitabine is a synthetic pyrimidine nucleoside analogue which is administered intravenously as a chemotherapeutic to treat numerous cancers
We have shown in both colon and pancreatic tumour cell lines that gemcitabine can upregulate the expression of Human leukocyte class I alleles, and NKG2D ligands MIC1 A/B and ULBP proteins [3,4]
Gemcitabine was first licensed to treat tumours in 1997 and is still used as first or second line chemotherapy, typically in tumours which are often non-responsive to immunotherapy such as checkpoint inhibition and are in urgent need of more efficacious anti-cancer therapies
Summary
The immune modulatory properties of gemcitabine make it a good candidate for combination with checkpoint inhibition immunotherapy for cancer such as pancreatic cancer with which immunotherapy has had limited success [19]. Most of the clinical studies to date are based on the treatment of pancreatic cancer, typically thought to be a non-immunologic tumour, and a good model with which to test agents intended to reverse immune inhibition and increase the infiltration of anti-tumour T-cell immune responses of the kind associated with checkpoint inhibitor responsiveness. Combinations of gemcitabine and checkpoint inhibition have for the most part proven ineffective when used to treat cancer patients (Table 1)
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