What is the name of the methodology?
The PDTF platform: Ex vivo culture of patient-derived tumor fragments
OI Name
Daniela Thommen
What is the methodology good for?
PDTFs are ~1mm3 sized tumor explants micro dissected from surgical tumor resections or biopsies from cancer patients. They can be used to functionally study different cell types and their interactions within the human tumor microenvironment and to investigate response or resistance to cancer treatments on patient tumor samples.
Figure created with Biorender.
Figure created with Biorender.
What is/are the main advantages of this methodology over related technologies?
PDTFs can be established for multiple cancer types. The fragments maintain the patient-specific native tumor microenvironment including diverse cancer, immune, and stromal cell populations, as well as their spatial organization and functionality. The cultures can be combined with multiple readout technologies (e.g., flow cytometry, bulk/single cell RNA-sequencing, proteomics, secretomics, etc.), though some adaptation for low cell numbers might be needed. Cryopreservation of PDTFs is feasible, allowing to biobank material and validate or in-depth explore findings within specific tumor samples.
What are the most important limitations of the methodology (1-3 sentences)?
PDTFs cannot be expanded, limiting analysis to the patient material available. We established this platform as a short-term culture (with cryopreserved PDTFs ~2 days, fresh ~5 days) to avoid tumor microenvironment modulation by growth factors or cytokines, limiting for instance assessment of epigenetic drugs or genetic manipulations.
What type of samples are compatible with methodology
Cancer cell lines | Primary cells in culture | Organoids | Primary tissue |
no | no | no | Yes |
What future develops to the methodology are you planning, in any?
We are currently exploiting different formats (e.g., larger slice-type models better suited for imaging) and the setup of invasion assays with exogenous immune cells (e.g., CAR T cells)
If someone outside your lab wants to use the methodology, what is the best option?
A) What do you need to provide them to make it work?
- Provide protocols (they can do it themselves if they have access to patient material)
- Train a person from their lab
- Perform the experiments in your lab, in collaboration
B) Is there any minimal expertise/equipment others need to work with the methodology?
Good tissue culture skills, feeling comfortable to work with patient material, required permits/training for the use of patient material and/or data, fast access to patient material if setup in own lab is envisioned (long transfer times from surgery theatre to lab may limit viability)
Name one or more people in your lab that are experienced with the methodology
Mercedes Machuca-Ostos ([email protected]) established the PDTF platform in a clinical trial setting
Mette Volkers ([email protected]) and Janniek Mors ([email protected]) can provide input on using PDTFs for investigating cancer treatments
All other members of the Thommen lab are experienced with the platform
Who originally developed the methodology (provide reference if applicable)?
The method has been developed by Paula Voabil, Marjolein de Bruijn and Lisanne Roelofsen (doi: 10.1038/s41591-021-01398-3, doi: 10.1016/j.xpro.2023.102282).