PT  - JOURNAL ARTICLE
AU  - Dinevska, Marija
AU  - Mcaloney, Lachlan
AU  - Widodo, Samuel S.
AU  - Filiz, Gulay
AU  - Anderson, Jeremy
AU  - Dworkin, Sebastian
AU  - Windley, Simon P.
AU  - Wilhelm, Dagmar
AU  - Mantamadiotis, Theo
TI  - Testicular sex cord–stromal tumors in mice with constitutive activation of PI3K and loss of Pten
AID  - 10.1101/2024.09.16.613175
DP  - 2024 Jan 01
TA  - bioRxiv
PG  - 2024.09.16.613175
4099  - http://biorxiv.org/content/early/2024/09/19/2024.09.16.613175.short
4100  - http://biorxiv.org/content/early/2024/09/19/2024.09.16.613175.full
AB  - Testicular tumors are the most common malignancy of young men and tumors affecting the testis are caused by somatic mutations in germ or germ-like cells. The PI3K pathway is constitutively activated in about one third of testicular cancers. To investigate the role of the PI3K pathway in transforming stem-like cells in the testis, we investigated tumors derived from mice with post-natal, constitutive activation of PI3K signaling and homozygous deletion of tumor suppressor Pten, targeted to nestin expressing cells. Mice developed aggressive tumors, exhibiting heterogeneous histopathology and hemorrhaging. The tumors resemble the rare testis tumor type, testicular sex cord–stromal Leydig cell tumors. Single cell resolution spatial tissue analysis demonstrated that T-cells are the dominant tumor infiltrating immune cell type, with very few infiltrating macrophages observed in the tumor tissue, with CD8+ T-cells predominating. Further analysis showed that immune cells preferentially localize to or accumulate within stromal regions.Competing Interest StatementThe authors have declared no competing interest.