Dinevska Marija, McAloney Lachlan, Widodo Samuel S, Filiz Gulay, Anderson Jeremy, Dworkin Sebastian, Windley Simon P, Wilhelm Dagmar, Mantamadiotis Theo
Department of Surgery (RMH), The University of Melbourne, Parkville, VIC 3052, Australia.
Department of Microbiology & Immunology, The University of Melbourne, Parkville, VIC 3052, Australia.
Carcinogenesis. 2025 Jan 20;46(1). doi: 10.1093/carcin/bgae077.
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.
睾丸肿瘤是年轻男性最常见的恶性肿瘤，影响睾丸的肿瘤是由生殖细胞或类生殖细胞中的体细胞突变引起的。约三分之一的睾丸癌中PI3K通路持续激活。为了研究PI3K通路在睾丸中转化干细胞样细胞的作用，我们研究了出生后PI3K信号通路组成性激活且肿瘤抑制基因Pten纯合缺失的小鼠所产生的肿瘤，这些基因靶向于表达巢蛋白的细胞。小鼠发生侵袭性肿瘤，表现出异质性组织病理学和出血。这些肿瘤类似于罕见的睾丸肿瘤类型，即睾丸性索间质Leydig细胞瘤。单细胞分辨率空间组织分析表明，T细胞是主要的肿瘤浸润免疫细胞类型，在肿瘤组织中观察到的浸润巨噬细胞很少，以CD8+ T细胞为主。进一步分析表明，免疫细胞优先定位于或聚集在间质区域。
