Dissecting the Immunosuppressive Tumor Microenvironment and Intercellular Communication in Testicular DLBCL via scRNA-seq

Testicular diffuse large B-cell lymphoma (TDLBL) is a rare, aggressive malignancy. This study aimed to explore the TDLBL tumor microenvironment (TME) and intercellular communication via single-cell RNA sequencing integrated with PBMC data. Bioinformatics analyses, supported by IHC and IF validation, suggested a complex immunosuppressive TME. Malignant B cells appeared to exhibit downregulated MHC-II expression, while T cells showed signs of exhaustion, potentially characterized by elevated PD-1, TIGIT, and apoptosis-related gene expression. Tumor-associated macrophages tended toward M2 polarization, with MRC1 expression potentially correlating with poor prognosis. Notably, Sertoli cells appeared to lose typical spermatogenic functions and may adopt immunomodulatory roles through interactions with effector T cells. Furthermore, the MIF-CD74 axis may constitute a pivotal immunosuppressive network. Collectively, our findings suggest that the TDLBL TME might be shaped by T cell exhaustion, M2 macrophage polarization, and altered Sertoli cell function, indicating that MRC1 could represent a promising prognostic biomarker for further investigation.