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Updated: Aug 10, 2026
A 3D Organotypic Melanoma Spheroid Skin Model
Published on: May 18, 2018
An organotypic human melanoma-in-skin model as an in vitro tool for testing Vγ9Vδ2-T cell-based immunotherapy
E Michielon1,2,3, L A King2,3,4, T Waaijman1,2
1Department of Molecular Cell Biology and Immunology, Amsterdam University Medical Center Location Vrije Universiteit Amsterdam, Amsterdam.
Background:
Despite considerable advancements in cancer immunotherapy, advanced melanoma still presents a substantial clinical challenge. In an effort to explore treatment options, we examined the immunotherapeutic potential of effector Vγ9Vδ2-T cells in vitro in a three-dimensional (3D) human organotypic melanoma-in-skin (Mel-RhS) model.
Materials And Methods:
Vγ9Vδ2-T cells were introduced into Mel-RhS via intradermal injection and cultured within the tissue microenvironment for up to 3 days.
Results:
Vγ9Vδ2-T cells remained viable for up to 3 days and were in close proximity to or within tumor nests. Upon Mel-RhS dissociation, a fraction was shown to be decorated by melanoma-associated chondroitin sulfate proteoglycan (MCSP), demonstrating their ability to actively navigate the tumor microenvironment and trogocytose cancer cells. Investigation into the apparent trogocytosis revealed an enhanced activated state of MCSP-decorated Vγ9Vδ2-T cells, evidenced by increased expression levels of 4-1BB, NKp44, programmed cell death protein-1 (PD-1), and programmed death-ligand 1 (PD-L1), compared with their MCSP- counterpart. These findings suggest that Vγ9Vδ2-T cells, upon successfully contacting melanoma cells, actively recognize and acquire MCSP from these malignant cells. Evidence of actual tumor cell elimination, although not significant, was only obtained after preincubation of Mel-RhS with pamidronate, a phosphoantigen-inducing agent, indicating the need for additional T cell receptor-mediated signaling for Vγ9Vδ2-T cells to reach their full oncolytic potential.
Conclusions:
This study highlights the viability and persistence of Vγ9Vδ2-T cells within the 3D microenvironment, their migratory and antitumor functionality, and the suitability of the model for testing T cell-based therapies, contributing both to the understanding of Vγ9Vδ2-T cell biology and their application in cancer immunotherapy.
Insights
Effector Vγ9Vδ2-T cells show viability and antitumor function in a 3D melanoma model. Further optimization is needed for significant tumor cell elimination in cancer immunotherapy.
Area of Science:
- Immunology
- Oncology
- Cell Biology
Background:
- Advanced melanoma remains a significant challenge in cancer immunotherapy.
- Exploring novel therapeutic strategies is crucial for improving patient outcomes.
Purpose of the Study:
- To investigate the immunotherapeutic potential of effector Vγ9Vδ2-T cells.
- To evaluate Vγ9Vδ2-T cell function in a 3D human organotypic melanoma-in-skin (Mel-RhS) model.
Main Methods:
- Vγ9Vδ2-T cells were introduced into the Mel-RhS model via intradermal injection.
- Cell viability, migration, and interaction with melanoma cells were assessed over 3 days.
- T cell activation markers and melanoma-associated chondroitin sulfate proteoglycan (MCSP) interaction were analyzed.
Main Results:
- Vγ9Vδ2-T cells remained viable and exhibited migratory capacity within the tumor microenvironment.
- MCSP-decorated Vγ9Vδ2-T cells showed an enhanced activated state, indicating interaction with melanoma cells.
- Limited tumor cell elimination was observed, suggesting a need for enhanced T cell receptor-mediated signaling.
Conclusions:
- The 3D Mel-RhS model is suitable for evaluating T cell-based therapies.
- Vγ9Vδ2-T cells demonstrate potential for melanoma immunotherapy due to their viability and functional activity.
- Further research is needed to optimize Vγ9Vδ2-T cell-mediated tumor elimination.
