Issue 20, 2018

3D microfluidic ex vivo culture of organotypic tumor spheroids to model immune checkpoint blockade

Abstract

Microfluidic culture has the potential to revolutionize cancer diagnosis and therapy. Indeed, several microdevices are being developed specifically for clinical use to test novel cancer therapeutics. To be effective, these platforms need to replicate the continuous interactions that exist between tumor cells and non-tumor cell elements of the tumor microenvironment through direct cell–cell or cell–matrix contact or by the secretion of signaling factors such as cytokines, chemokines and growth factors. Given the challenges of personalized or precision cancer therapy, especially with the advent of novel immunotherapies, a critical need exists for more sophisticated ex vivo diagnostic systems that recapitulate patient-specific tumor biology with the potential to predict response to immune-based therapies in real-time. Here, we present details of a method to screen for the response of patient tumors to immune checkpoint blockade therapy, first reported in Jenkins et al. Cancer Discovery, 2018, 8, 196–215, with updated evaluation of murine- and patient-derived organotypic tumor spheroids (MDOTS/PDOTS), including evaluation of the requirement for 3D microfluidic culture in MDOTS, demonstration of immune-checkpoint sensitivity of PDOTS, and expanded evaluation of tumor–immune interactions using RNA-sequencing to infer changes in the tumor–immune microenvironment. We also examine some potential improvements to current systems and discuss the challenges in translating such diagnostic assays to the clinic.

Graphical abstract: 3D microfluidic ex vivo culture of organotypic tumor spheroids to model immune checkpoint blockade

Article information

Article type
Paper
Submitted
29 มี.ค. 2561
Accepted
22 ส.ค. 2561
First published
05 ก.ย. 2561
This article is Open Access
Creative Commons BY-NC license

Lab Chip, 2018,18, 3129-3143

3D microfluidic ex vivo culture of organotypic tumor spheroids to model immune checkpoint blockade

A. R. Aref, M. Campisi, E. Ivanova, A. Portell, D. Larios, B. P. Piel, N. Mathur, C. Zhou, R. V. Coakley, A. Bartels, M. Bowden, Z. Herbert, S. Hill, S. Gilhooley, J. Carter, I. Cañadas, T. C. Thai, S. Kitajima, V. Chiono, C. P. Paweletz, D. A. Barbie, R. D. Kamm and R. W. Jenkins, Lab Chip, 2018, 18, 3129 DOI: 10.1039/C8LC00322J

This article is licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported Licence. You can use material from this article in other publications, without requesting further permission from the RSC, provided that the correct acknowledgement is given and it is not used for commercial purposes.

To request permission to reproduce material from this article in a commercial publication, please go to the Copyright Clearance Center request page.

If you are an author contributing to an RSC publication, you do not need to request permission provided correct acknowledgement is given.

If you are the author of this article, you do not need to request permission to reproduce figures and diagrams provided correct acknowledgement is given. If you want to reproduce the whole article in a third-party commercial publication (excluding your thesis/dissertation for which permission is not required) please go to the Copyright Clearance Center request page.

Read more about how to correctly acknowledge RSC content.

Social activity

Spotlight

Advertisements