Goulart MR, Stasinos K, Fincham REA, Delvecchio FR, Kocher HM. T cells in pancreatic cancer stroma. World J Gastroenterol 2021; 27(46): 7956-7968 [PMID: 35046623 DOI: 10.3748/wjg.v27.i46.7956]
Corresponding Author of This Article
Hemant M Kocher, FRCS (Gen Surg), MBBS, MD, MS, Professor, Centre for Tumour Biology Barts Cancer Institute-A CRUK Centre of Excellence, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ, United Kingdom. h.kocher@qmul.ac.uk
Research Domain of This Article
Oncology
Article-Type of This Article
Minireviews
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (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/
World J Gastroenterol. Dec 14, 2021; 27(46): 7956-7968 Published online Dec 14, 2021. doi: 10.3748/wjg.v27.i46.7956
T cells in pancreatic cancer stroma
Michelle R Goulart, Konstantinos Stasinos, Rachel Elizabeth Ann Fincham, Francesca R Delvecchio, Hemant M Kocher
Michelle R Goulart, Konstantinos Stasinos, Rachel Elizabeth Ann Fincham, Francesca R Delvecchio, Hemant M Kocher, Centre for Tumour Biology Barts Cancer Institute-A CRUK Centre of Excellence, Queen Mary University of London, London EC1M 6BQ, United Kingdom
Konstantinos Stasinos, Hemant M Kocher, Barts and the London HPB Centre, The Royal London Hospital, Barts Health NHS Trust, London E1 1BB, United Kingdom
Francesca R Delvecchio, Centre for Experimental Medicine and Rheumatology, William Harvey Research Institute, Queen Mary University of London, London EC1M 6BQ, United Kingdom
Author contributions: Goulart MR and drafted the original manuscript and composed the original figure; Goulart MR, Stasinos K, Fincham REA, Delvecchio FR and Kocher HM contributed to the review and editing of the manuscript and figure.
Supported byPCRF Post-doctoral Fellowship (to Goulart MR); Lewin International Surgical Oncology Fellowship funded by Barts Health NHS Trust and Barts Charity(to Stasinos K); PhD Studentship Awarded by Barts Charity (London, UK) and A*STAR (Singapore) (to Fincham REA); and Cancer Research UK Post-doctoral Fellowship (to Delvecchio FR).
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: https://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-A CRUK Centre of Excellence, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ, United Kingdom. h.kocher@qmul.ac.uk
Received: April 9, 2021 Peer-review started: April 9, 2021 First decision: May 17, 2021 Revised: May 18, 2021 Accepted: November 28, 2021 Article in press: November 28, 2021 Published online: December 14, 2021
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is a highly devastating disease with a dismal 5-year survival rate. PDAC has a complex tumour microenvironment; characterised by a robust desmoplastic stroma, extensive infiltration of immunesuppressive cells such as immature myeloid cells, tumour-associated macrophages, neutrophils and regulatory T cells, and the presence of exhausted and senescent T cells. The cross-talk between cells in this fibrotic tumour establishes an immune-privileged microenvironment that supports tumour cell escape from immune-surveillance, disease progression and spread to distant organs. PDAC tumours, considered to be non-immunogenic or cold, express low mutation burden, low infiltration of CD8+ cytotoxic lymphocytes that are localised along the invasive margin of the tumour border in the surrounding fibrotic tissue, and often display an exhausted phenotype. Here, we review the role of T 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 T cells as therapy.
Core Tip: Pancreatic ductal adenocarcinoma (PDAC) is a highly devastating disease with a dismal 5-year survival of less than 5% in patients with metastatic disease, and is predicted to become the second cause of cancer-related death by 2030. Here, we discuss the complexity of the PDAC immunosuppressive tumour microenvironment, the mechanisms involved in T cell dysfunction, and potential immunotherapeutic strategies for treating PDAC.
