Microfluidic technologies for immunotherapy studies on solid tumours

Paterson, K., Zanivan, S. , Glasspool, R., Coffelt, S.B. and Zagnoni, M. (2021) Microfluidic technologies for immunotherapy studies on solid tumours. Lab on a Chip, 21(12), pp. 2306-2329. (doi: 10.1039/D0LC01305F) (PMID:34085677) (PMCID:PMC8204114)

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Abstract

Immunotherapy is a powerful and targeted cancer treatment that exploits the body's immune system to attack and eliminate cancerous cells. This form of therapy presents the possibility of long-term control and prevention of recurrence due to the memory capabilities of the immune system. Various immunotherapies are successful in treating haematological malignancies and have dramatically improved outcomes in melanoma. However, tackling other solid tumours is more challenging, mostly because of the immunosuppressive tumour microenvironment (TME). Current in vitro models based on traditional 2D cell monolayers and animal models, such as patient-derived xenografts, have limitations in their ability to mimic the complexity of the human TME. As a result, they have inadequate translational value and can be poorly predictive of clinical outcome. Thus, there is a need for robust in vitro preclinical tools that more faithfully recapitulate human solid tumours to test novel immunotherapies. Microfluidics and lab-on-a-chip technologies offer opportunities, especially when performing mechanistic studies, to understand the role of the TME in immunotherapy, and to expand the experimental throughput when using patient-derived tissue through its miniaturization capabilities. This review first introduces the basic concepts of immunotherapy, presents the current preclinical approaches used in immuno-oncology for solid tumours and then discusses the underlying challenges. We provide a rationale for using microfluidic-based approaches, highlighting the most recent microfluidic technologies and methodologies that have been used for studying cancer–immune cell interactions and testing the efficacy of immunotherapies in solid tumours. Ultimately, we discuss achievements and limitations of the technology, commenting on potential directions for incorporating microfluidic technologies in future immunotherapy studies.

Item Type:Articles
Additional Information:This work was funded by core grants from Cancer Research UK (A31287, A29800 and A18076 to S. R. Z., A25142 to S. B. C.), Breast Cancer Now (2019AugPR1307 to S. R. Z, 2018JulPR1101 and 2019DecPhD1349 to S. B. C.), the Wellcome Trust (208990/Z/17/Z to S. B. C.), the Medical Research Council (MR/R502327/1 to S. B. C.), Tenovus Scotland (S17-17 to S. B. C.), AMS Biotechnology Europe Ltd (industrial PhD studentship to K. P. and M. Z.) and internal funds by Strathclyde University to M. Z. and K. P.
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Coffelt, Dr Seth and Zanivan, Professor Sara and Glasspool, Dr Rosalind
Authors: Paterson, K., Zanivan, S., Glasspool, R., Coffelt, S.B., and Zagnoni, M.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cancer Sciences
Journal Name:Lab on a Chip
Publisher:Royal Society of Chemistry
ISSN:1473-0197
ISSN (Online):1473-0189
Published Online:04 June 2021
Copyright Holders:Copyright © 2021 The Royal Society of Chemistry
First Published:First published in Lab on a Chip 21(12): 2306-2329
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
190874CR-UK Centre renewalKaren VousdenCancer Research UK (CRUK)C596/A18076Institute of Cancer Sciences
174115CRUK Centre RenewalOwen SansomCancer Research UK (CRUK)C7932/A25142CS - Beatson Institute for Cancer Research
303457Regulation of IL-17-producing T cells in Breast Cancer MetastasisSeth CoffeltBreast Cancer Now (BRCANNOW)2018JulPR1101CS - Beatson Institute for Cancer Research
301010understanding gamma delta T cell function in colorectal cancer metastasisSeth CoffeltWellcome Trust (WELLCOTR)208990/Z/17/ZCS - Beatson Institute for Cancer Research
313949National Productivity Investment Fund StudentshipsGeorge BaillieMedical Research Council (MRC)MR/R502327/1MVLS - Graduate School
301837Insights into the behaviour of anti-metastatic T cellsSeth CoffeltTenovus Scotland (TENOVUS)S17-17CS - Beatson Institute for Cancer Research