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Single-cell transcriptomic analysis reveals that the APP-CD74 axis promotes immunosuppression and progression of

Guo Chen1, Wei Wang2, Xin Wei2

  • 1Department of Urology/Pelvic Floor and Andrology, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, PR China.

The Journal of Pathology
|August 20, 2024
PubMed

Insights

This study reveals significant intra-tumoral heterogeneity in testicular tumors, identifying specific malignant subclusters linked to immunosuppression and poorer survival. Key cell-cell interactions like APP-CD74 are highlighted, offering new therapeutic targets.

Area of Science:

  • Oncology
  • Molecular Biology
  • Immunology

Background:

  • Testicular tumors are the most common malignancy in young men, yet their pathogenesis and molecular mechanisms are poorly understood.
  • Understanding tumor heterogeneity and the tumor microenvironment is crucial for developing effective targeted therapies.

Purpose of the Study:

  • To delineate intra-tumoral heterogeneity in testicular tumors.
  • To characterize the intercellular communication network within the tumor microenvironment.
  • To identify molecular targets for novel therapeutic strategies.

Main Methods:

  • Single-cell RNA sequencing analysis of 40,760 transcriptomes from seminomas, mixed germ cell tumors, Leydig cell tumors, and healthy donors.
  • Identification and characterization of malignant subclusters and immune cell subpopulations.
  • Analysis of cellular communication pathways and gene expression alterations in somatic cells.

Main Results:

  • Five distinct malignant subclusters were identified, with subclusters 1 and 3 associated with an immunosuppressive state and worse disease-free survival.
  • APP-CD74 interactions were significantly enhanced between malignant subclusters and immune cells.
  • Aberrant spermatogenesis and global gene alterations in somatic cells, particularly Sertoli cells, were observed in seminoma testes, disrupting communication with spermatogonial stem cells.

Conclusions:

  • The study provides a comprehensive delineation of intra-tumoral heterogeneity and the tumor immune microenvironment in testicular tumors.
  • Identification of specific malignant subclusters and intercellular communication pathways offers novel insights for targeted therapeutic interventions.
  • Disturbed cellular communication involving Sertoli cells highlights their critical role in seminoma pathogenesis.
Keywords:
APP‐CD74Leydig cell tumorSertoli cellcellular communicationimmune microenvironmentintra‐tumoral heterogeneitymixed germ cell tumorseminomasingle‐cell analysistesticular tumor

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