Immunological combination treatment holds the key to improving survival in pancreatic cancer
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REVIEW – CLINICAL ONCOLOGY
Immunological combination treatment holds the key to improving survival in pancreatic cancer M. H. Sodergren1 · N. Mangal1 · H. Wasan1 · A. Sadanandam2,3 · V. P. Balachandran4,5,6 · L. R. Jiao1 · N. Habib1 Received: 14 May 2020 / Accepted: 22 July 2020 © The Author(s) 2020
Abstract Advances in surgery, peri-operative care and systemic chemotherapy have not significantly improved the prognosis of pancreatic cancer for several decades. Early clinical trials of immunotherapy have yielded disappointing results proposing other means by which the tumour microenvironment serves to decrease the immune response. Additionally, the emergence of various subtypes of pancreatic cancer has emerged as a factor for treatment responses with immunogenic subtypes carrying a better prognosis. Herein we discuss the reasons for the poor response to checkpoint inhibitors and outline a rationale why combination treatments are likely to be most effective. We review the therapies which could provide optimal synergistic effects to immunotherapy including chemotherapy, agents targeting the stroma, co-stimulatory molecules, vaccinations and methods of immunogenic tumour priming including radiofrequency ablation. Finally, we discuss reasons why peri-operative and in particular neoadjuvant combination treatments are likely to be most effective and should be considered for early clinical trials. Keywords Combination · Immunotherapy · Pancreatic · Cancer
Introduction Pancreatic ductal adenocarcinoma (PDAC) has a dismal prognosis and despite advances in surgical, anaesthetic and perioperative techniques, this has not significantly changed in the last half a century, and by 2030 PDAC is expected to become the second most common cause of death from cancer in the United States (Rahib et al. 2014). The high * M. H. Sodergren [email protected] 1
Department of Surgery and Cancer, Imperial College London, Hammersmith Campus, DuCane Road, London W12 0HS, UK
2
Division of Molecular Pathology, Institute for Cancer Research, London, UK
3
Centre for Molecular Pathology, Royal Marsden Hospital, London, UK
4
Hepatopancreatobiliary Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, USA
5
Parker Institute for Cancer Immunotherapy, Memorial Sloan Kettering Cancer Center, New York, USA
6
David M. Rubenstein Center for Pancreatic Cancer Research, Memorial Sloan Kettering Cancer Center, New York, USA
mortality is related to the proportion of patients that are diagnosed at a relatively late stage and in the 20% of patients who present with localised disease, the vast majority will develop recurrent disease following surgical resection. Although there have been encouraging non-randomised data relating to neoadjuvant FOLFIRINOX treatment, the fact is that PDAC is resistant to traditional chemotherapeutic agents currently available in clinical practice (Marsh et al. 2015). It is unlikely that significant further progress will be made in the technical surgical management of PD
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