Primary testicular diffuse large B-cell lymphomas (PT-DLBCL), the most prevalent subtype of testicular lymphoma, occurs in an immune-privileged site within the testis. Although advances in genomic technologies have resulted in remarkable progress in understanding the pathogenesis of DLBCLs, the characterization of the tumor microenvironment (TME) and spatial organization of PT-DLBCL remains unclear.

This research, published in the Genes & Diseases journal by a team from Zhejiang University, Nantong University, Shanghai Jiao Tong University and Singleron Biotechnologies Ltd., utilized single-cell RNA sequencing (scRNA-seq) and spatial transcriptomics to identify the tissue architecture of PT-DLBCL.

The initial investigation involved profiling of the transcriptomes of 19,559 single cells derived from a PT-DLBCL patient via scRNA-seq. The results revealed that the PT-DLBCL TME was predominantly composed of three exhausted CD8⁺ T cell subpopulations and two B cell subpopulations. Further analysis by the research team revealed significant genetic heterogeneity, providing a deeper understanding of the tumor’s cellular diversity.

Interestingly, the researchers noted that B1 cells constituted 16% of the TME and exhibited a clustered distribution, suggesting a role in tumor progression through distant metastasis. Moreover, inhibition of critical transcription factors, E2F and CREB, reduced cell proliferation, induced apoptosis in human B-lymphoma cells, and inhibited tumor growth in testicular DLBCL xenograft models, underscoring their potential as novel therapeutic targets.

Using chromatin immunoprecipitation sequencing (ChIP-seq), this study identified the enriched loci of E2F and CREB that regulate human B-lymphoma cell proliferation and apoptosis. Additionally, spatial transcriptomics unveiled the spatial architecture of the TME in DLBCL, where exhausted T cells were strategically positioned around tumor B cells, while macrophages formed an outer ring, encircling the exhausted T cells. Concurrently, the researchers also delineated the expression patterns of key genes such as MALAT1, RPS3A, RPS7, RPS23, RPS27A, IGHM, HINT1, and HSPA8 across various regions.

Despite significant findings, this study has certain limitations, including the use of single patient samples and uneven experimental group sizes. Nonetheless, this study offers insight into the tumorigenic progression mechanisms and potential novel therapeutic opportunities associated with PT-DLBCL.

Reference

Title of Original Paper: The integration of single-cell RNA sequencing and spatial transcriptomics reveals the tumor microenvironment and spatial organization of testicular diffuse large B-cell lymphomas

Journal: Genes & Diseases

Genes & Diseases is a journal for molecular and translational medicine. The journal primarily focuses on publishing investigations on the molecular bases and experimental therapeutics of human diseases. Publication formats include full length research article, review article, short communication, correspondence, perspectives, commentary, views on news, and research watch.

DOI: https://doi.org/10.1016/j.gendis.2024.101475

Funding Information:

The National Natural Science Foundation of China (No. 82371613, No. 82171611, No. 81971376 and No. 82401864)
The Key Research and Development Program of Zhejiang Province (No. 2023C03035)
The Key Research and Development Program of Ningxia Hui Autonomous Region (No. 2021BEG02029)

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Genes & Diseases publishes rigorously peer-reviewed and high quality original articles and authoritative reviews that focus on the molecular bases of human diseases. Emphasis is placed on hypothesis-driven, mechanistic studies relevant to pathogenesis and/or experimental therapeutics of human diseases. The journal has worldwide authorship, and a broad scope in basic and translational biomedical research of molecular biology, molecular genetics, and cell biology, including but not limited to cell proliferation and apoptosis, signal transduction, stem cell biology, developmental biology, gene regulation and epigenetics, cancer biology, immunity and infection, neuroscience, disease-specific animal models, gene and cell-based therapies, and regenerative medicine.

Scopus CiteScore: 7.3 | Impact Factor: 6.9

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