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Updated: Jun 12, 2025
Author Spotlight: Recreating Melanoma Complexity with Patient-Derived Organoids for Immunotherapy Evaluation
Published on: September 6, 2024
Unveiling Therapeutic Opportunities with Melanoma Patient-derived Organoid Models
Beatriz Goncalves1, Shujing Liu1, Xiaogang Zhang1
1Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania.
Abstract:
With the development of immunotherapy, there is an ongoing need to develop models that can recapitulate the tumor microenvironment of native tumors. While traditional two- and three-dimensional models can offer insights into cancer development and progression, these lack crucial aspects that hinder a faithful mimic of native tumors. An alternative model that has gained a lot of attention is the patient-derived organoid. The development of these organoids recapitulates the complex intercellular communication, tumor microenvironment, and histoarchitecture of tumors. This paper describes the protocol for establishing melanoma patient-derived organoid (MPDO) models. To validate these models, we assessed the immune cell composition, including the expression levels of T-cell activation markers, to confirm the cellular heterogeneity of the organoids. Additionally, to describe the potential utility of MPDOs in cellular therapies, we evaluated the cytotoxic capabilities of treating the organoids with γδ T-cells. In conclusion, the MPDO models offer promising avenues for understanding tumor complexity, validating therapeutic strategies, and potentially advancing personalized treatment.
Insights
Patient-derived organoids (MPDOs) accurately model the melanoma tumor microenvironment, including immune cell composition. These models show promise for testing immunotherapies like γδ T-cell treatments and advancing personalized cancer care.
Area of Science:
- Oncology
- Immunotherapy
- Cancer Modeling
Background:
- Traditional cancer models lack the complexity of the native tumor microenvironment.
- Patient-derived organoids (MPDOs) offer a more faithful recapitulation of tumor complexity.
- There is a need for advanced models to study immunotherapy efficacy.
Purpose of the Study:
- To describe the protocol for establishing melanoma patient-derived organoid (MPDO) models.
- To validate MPDOs by assessing immune cell composition and heterogeneity.
- To evaluate the potential of MPDOs in testing cellular therapies, specifically γδ T-cells.
Main Methods:
- Established melanoma patient-derived organoid (MPDO) models.
- Assessed immune cell composition and T-cell activation markers within MPDOs.
- Evaluated the cytotoxic effects of γδ T-cells on MPDOs.
Main Results:
- MPDOs successfully recapitulated tumor microenvironment complexity and cellular heterogeneity.
- Immune cell composition, including T-cell activation, was confirmed in MPDOs.
- MPDOs demonstrated utility in evaluating the efficacy of γδ T-cell therapy.
Conclusions:
- MPDO models provide a promising platform for understanding tumor complexity.
- These models can be used to validate therapeutic strategies, including immunotherapy.
- MPDOs hold potential for advancing personalized melanoma treatment.
