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World J Gastroenterol. Jun 28, 2021; 27(24): 3483-3501
Published online Jun 28, 2021. doi: 10.3748/wjg.v27.i24.3483
Natural killer cells in pancreatic cancer stroma
Rachel Elizabeth Ann Fincham, Francesca Romana Delvecchio, Michelle R Goulart, Joe Poe Sheng Yeong, Hemant M Kocher
Rachel Elizabeth Ann Fincham, Francesca Romana Delvecchio, Michelle R Goulart, Barts Cancer Institute-CRUK Centre of Excellence, Queen Mary University of London, London EC1M 6BQ, United Kingdom
Joe Poe Sheng Yeong, Institute of Molecular and Cellular Biology, Agency for Science, Technology and Research, Singapore 138673, Singapore
Hemant M Kocher, Centre for Tumour Biology, Barts Cancer Institute-CRUK Centre of Excellence, Queen Mary University of London, London EC1M 6BQ, United Kingdom
Author contributions: Fincham REA and Kocher HM drafted the original manuscript; Fincham REA composed the original figures; Fincham REA, Delvecchio FR, Goulart MR, Yeong JPS and Kocher HM contributed to the review and editing of the manuscript and figures.
Supported by the PhD Studentship Awarded by Barts Charity (London, United Kingdom) and A*STAR (Singapore); the Cancer Research UK Post-doctoral Fellowship; and the PCRF Post-doctoral Fellowship.
Conflict-of-interest statement: The authors declare no conflicts of interest.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Hemant M Kocher, FRCS (Gen Surg), MBBS, MD, MS, Professor, Centre for Tumour Biology, Barts Cancer Institute-CRUK Centre of Excellence, Queen Mary University of London, John Vane Science Centre, Charterhouse Square, London, EC1M 6BQ, United Kingdom. h.kocher@qmul.ac.uk
Received: February 1, 2021
Peer-review started: February 1, 2021
First decision: May 1, 2021
Revised: May 6, 2021
Accepted: May 25, 2021
Article in press: May 25, 2021
Published online: June 28, 2021
Processing time: 144 Days and 0.1 Hours
Abstract

Pancreatic cancer remains one of medicine’s largest areas of unmet need. With five-year survival rates of < 8%, little improvement has been made in the last 50 years. Typically presenting with advance stage disease, treatment options are limited. To date, surgery remains the only potentially curative option, however, with such late disease presentation, the majority of patients are unresectable. Thus, new therapeutic options and a greater understanding of the complex stromal interactions within the tumour microenvironment are sorely needed to revise the dismal outlook for pancreatic cancer patients. Natural killer (NK) cells are crucial effector units in cancer immunosurveillance. Often used as a prognostic biomarker in a range of malignancies, NK cells have received much attention as an attractive target for immunotherapies, both as cell therapy and as a pharmaceutical target. Despite this interest, the role of NK cells in pancreatic cancer remains poorly defined. Nevertheless, increasing evidence of the importance of NK cells in this dismal prognosis disease is beginning to come to light. Here, we review the role of NK cells in pancreatic cancer, examine the complex interactions of these crucial effector units within pancreatic cancer stroma and shed light on the increasingly attractive use of NK cells as therapy.

Keywords: Pancreatic cancer; Natural killer cells; Tumour microenvironment; Pancreatic cancer stroma; Stromal cells

Core Tip: Increasing evidence has found natural killer (NK) cells to be crucial players in the prognosis and progression of cancer. Whilst pancreatic cancer remains one of medicine’s largest areas of unmet need, NK cells may prove to be an exciting new therapeutic option for pancreatic cancer patients. Here we provide an overview of the complex interactions between NK cells and pancreatic cancer stroma, suggest a role for NK cells as prognostic biomarkers and highlight exciting new NK cell-based treatment options which may transform the therapeutic landscape of pancreatic cancer.