Email
Call
  • VT-iSIM
  • System Integration
  • VT-Infinity4
  • Resources
  • Applications
  • Company
Contact
  • VT-iSIM
  • System Integration
  • VT-Infinity4
  • Resources
  • Applications
  • Company
  • Contact

Engineering T cells to enhance 3D migration through structurally and mechanically complex tumor microenvironments

Posted on 16/07/2021

Authors: Erdem D. Tabdanov 1,2,3#, Nelson J. Rodríguez-Merced 1,2, Alexander X. Cartagena-Rivera 4, Vikram V. Puram 1,2,5, Mackenzie K. Callaway 1,2, Ethan A. Ensminger 1,2, Emily J. Pomeroy 6,7,8, Kenta Yamamoto 6,7,8, Walker S. Lahr 6,7, Beau R. Webber 6,7,8,9, Branden S. Moriarity 6,7,8,9, Alexander S. Zhovmer 10 and Paolo P. Provenzano 1,2,6,9,11#

Defining the principles of T cell migration in structurally and mechanically complex tumor microenvironments is critical to understanding sanctuaries from antitumor immunity and optimizing T cell-related therapeutic strategies. To enhance T cell migration through complex microenvironments, we engineered nanotextured platforms that allowed us to define how the balance between T cell phenotypes influences migration in response to tumor-mimetic structural and mechanical cues and characterize a mechanical optimum for migration that can be perturbed by manipulating an axis between microtubule stability and force generation. In 3D environments and live tumors, we demonstrate that microtubules instability, leading to increased Rho pathway-dependent cell contractility, promotes migration while clinically used microtubule-targeting chemotherapies profoundly decrease effective migration. Indeed, we show that rational manipulation of the microtubule-contractility axis, either pharmacologically or through genome engineering, results in engineered T cells that more effectively move through and interrogate 3D matrix and tumor volumes. This suggests that engineering cells to better navigate through 3D microenvironments could be part of an effective strategy to enhance efficacy of immune therapeutics.

doi: https://doi.org/10.1101/2020.04.21.051615

Previous Post
Anchoring cortical granules in the cortex ensures trafficking to the plasma membrane for post-fertilization exocytosis
Next Post
Microparticle traction force microscopy reveals subcellular force exertion patterns in immune cell–target interactions

Recent Posts

  • A new experimental platform facilitatesassessment of the transcriptional and chromatin landscapes of aging yeast 20/08/2021
  • Transbilayer Movement of Sphingomyelin Precedes Catastrophic Breakage of Enterobacteria-Containing Vacuoles 16/07/2021
  • Microtubule-directed transport of purine metabolons drives their cytosolic transit to mitochondria 16/07/2021
  • Microparticle traction force microscopy reveals subcellular force exertion patterns in immune cell–target interactions 16/07/2021
  • Engineering T cells to enhance 3D migration through structurally and mechanically complex tumor microenvironments 16/07/2021

Categories

  • Cell Biology (18)
  • Colloidal Dynamics (1)
  • Developmental Biology (10)
  • Genomics and Proteomics (3)
  • Neuroscience (3)
  • Physiology (2)

Contact us

Get in touch

sales@visitech.co.uk
+44 (0)191 516 6255
VisiTech International Ltd

Unit 92
Silverbriar
Sunderland Enterprise Park (East)
Sunderland
SR5 2TQ
UK

Follow us @visitech_uk

Send an Enquiry

Fill out this field
Please enter a valid email address.
Fill out this field
Fill out this field

© 2022 VisiTech International. Website from dodio.