What does this research mean for the field?

A PRMT5 MTA inhibitor enhances immunotherapy response in chromosome 9p21.3-deleted osteosarcoma models. Novelty: ClaimNovelty.NOVEL_FINDING. Consensus alignment: ConsensusAlignment.NEUTRAL.

What question did this study set out to answer?

This research aims to create a biobank for osteosarcoma models that enhances understanding of immune responses to therapy.

March 3, 2026Open Access

Reconstruction of T cell infiltration in an osteosarcoma PDX-organoid interactive biobank for personalized immunotherapy

Key Points

This research aims to create a biobank for osteosarcoma models that enhances understanding of immune responses to therapy.
Established individualized osteosarcoma organoids from patient-derived xenografts (PDXs).
Validated organoid models through histopathology, spatial features, and genomic analyses.
Reconstructed T cell infiltration in organoid models to assess immune responses.
Evaluated the impact of a PRMT5 inhibitor on immunotherapy response in specific osteosarcoma cases.
Individualized osteosarcoma organoids successfully mimic the tumor's structure and behavior.
T cell infiltration was effectively reconstructed in PDX-derived organoid models.
The PRMT5 inhibitor significantly improved immunotherapy outcomes in chromosome 9p21.3-deleted osteosarcoma cases.

Abstract

Osteosarcoma (OS) is an aggressive malignant bone tumor with limited therapeutic options and low response to immunotherapy. OS rarity slows clinical translation, highlighting the need for models that bridge patient-derived xenograft (PDX) systems and next-generation platforms. Here, we establish an OS PDX-organoid interactive biobank by self-assembling single-cell suspensions into individualized OS organoids (iOSs). iOS models recapitulate OS spatial and architectural features at millimeter scale in vitro and as xenografts and maintain functional pairing with matched PDX models. We validate iOS fidelity using histopathology, spatial features, genomics, transcriptomics, and pharmacogenomics. By reconstructing T cell infiltration in PDX-derived iOS models, we model treatment-associated immune responses and support immunotherapy translational studies. Using paired iOS-PDX models, we show that a PRMT5MTA inhibitor enhances immunotherapy response in chromosome 9p21.3-deleted OS.

Reconstruction of T cell infiltration in an osteosarcoma PDX-organoid interactive biobank for personalized immunotherapy

Key Points

Abstract

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