睾丸肿瘤是年轻男性中最常见的恶性肿瘤。然而，睾丸肿瘤的发病机制和分子基础在很大程度上仍然难以捉摸。我们的目的是描绘肿瘤微环境中复杂的肿瘤内异质性和细胞间通讯网络。总共分析了 40,760 个单细胞转录组，包括来自 6 名精原细胞瘤患者、两名混合生殖细胞肿瘤患者、一名 Leydig 细胞肿瘤患者和三名健康捐赠者的样本。在构建的景观中发现了五个不同的恶性亚群。其中，恶性 1 和 3 亚群与更严重的免疫抑制状态相关，并且表现出更差的无病生存率。进一步分析发现，恶性 1 和 3 亚群以及 14 种免疫亚群之间的 APP-CD74 相互作用显着增强。此外，我们建立了异常的精子发生轨迹，并描述了精原细胞瘤睾丸中体细胞的整体基因改变。支持细胞被认为是健康供体与精原细胞瘤睾丸之间差异最大的体细胞类型。睾丸精原细胞瘤中精原干细胞和支持细胞之间的细胞通讯受到干扰。我们的研究描述了睾丸肿瘤的肿瘤内异质性和肿瘤免疫微环境，为靶向治疗提供了新的见解。 © 2024 作者。约翰·威利出版的《病理学杂志》

Testicular tumors represent the most common malignancy among young men. Nevertheless, the pathogenesis and molecular underpinning of testicular tumors remain largely elusive. We aimed to delineate the intricate intra-tumoral heterogeneity and the network of intercellular communication within the tumor microenvironment. A total of 40,760 single-cell transcriptomes were analyzed, encompassing samples from six individuals with seminomas, two patients with mixed germ cell tumors, one patient with a Leydig cell tumor, and three healthy donors. Five distinct malignant subclusters were identified in the constructed landscape. Among them, malignant 1 and 3 subclusters were associated with a more immunosuppressive state and displayed worse disease-free survival. Further analysis identified that APP-CD74 interactions were significantly strengthened between malignant 1 and 3 subclusters and 14 types of immune subpopulations. In addition, we established an aberrant spermatogenesis trajectory and delineated the global gene alterations of somatic cells in seminoma testes. Sertoli cells were identified as the somatic cell type that differed the most from healthy donors to seminoma testes. Cellular communication between spermatogonial stem cells and Sertoli cells is disturbed in seminoma testes. Our study delineates the intra-tumoral heterogeneity and the tumor immune microenvironment in testicular tumors, offering novel insights for targeted therapy. © 2024 The Author(s). The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.© 2024 The Author(s). The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.