The following is a summary of “Genomic profiling of subcutaneous patient-derived xenografts reveals immune constraints on tumor evolution in childhood solid cancer,” published in the November 2023 issue of Oncology by He et al.
The research established a vital resource of 68 early-stage patient-derived xenografts (PDXs) derived from pediatric solid tumors in 65 patients. By conducting a thorough genomic examination of both patient tumors (PTs) and their corresponding PDX models, the researchers unveiled a notable discovery: roughly 30% of PT/PDX pairs showed limited mutation similarity. Upon closer inspection through clonal analysis, the study group unearthed an intriguing observation. In these discordant pairs, a minor but aggressive subclone from the patient’s tumor was the instigator, giving rise to the dominant clone within the PDX model. What’s particularly striking about this subclone is its heightened immunogenicity, suggesting a potential suppression by the immune system within the patient’s original tumor environment.
These findings suggest a fascinating correlation between the complexities of intratumoral diversity and the immune response’s interplay. This interaction contributes to the genetic disparities between patient tumors and their corresponding PDX models.
Furthermore, their investigation highlighted an encouraging aspect: PDX models generally exhibited remarkable similarity to the original patient tumors regarding copy number alterations and transcriptomic profiles. Additionally, their study identified a novel gene fusion, LRPAP1-PDGFRA, shedding light on previously undiscovered genomic characteristics within childhood solid tumors.
The study’s significant contributions lie in establishing a critical repository of PDX models for childhood cancers. Furthermore, it underscores the profound influence of immune dynamics on the evolution and development of tumors, elucidating the intricate relationship between tumor heterogeneity and immune responses in shaping the genetic landscape of these malignancies.
Source: nature.com/articles/s41467-023-43373-1
