Single-cell RNA sequencing uncovers heterogeneous transcriptional signatures in tumor-infiltrated dendritic cells in prostate cancer

Prostate cancer (PCa) is one of the two solid malignancies in which a higher T cell infiltration in the tumor microenvironment (TME) corresponds with a worse prognosis for the tumor. The inability of T cells to eliminate tumor cells despite an increase in their number reinforces the possibility of impaired antigen presentation. In this study, we investigated the TME at single-cell resolution to understand the molecular function and communication of dendritic cells (DCs) (as professional antigen-presenting cells). According to our data, tumor cells stimulate the migration of immature DCs to the tumor site by inducing inflammatory chemokines. Many signaling pathways such as TNF-alpha/NF-kappa B, IL2/STAT5, and E2F up-regulated after DCs enter the tumor location. In addition, some molecules such as GPR34 and SLCO2B1 decreased on the surface of DCs. The analysis of molecular and signaling alterations in DCs revealed some suppression mechanisms of tumors, such as removing mature DCs, reducing the DC's survival, inducing anergy or exhaustion in the effector T cells, and enhancing the differentiation of T cells to Th2 and Tregs. In addition, we investigated the cellular and molecular communication between DCs and macrophages in the tumor site and found three molecular pairs including CCR5/CCL5, CD52/ SIGLEC10, and HLA-DPB1/TNFSF13B. These molecular pairs are involved in the migration of immature DCs to the TME and disrupt the antigen-presenting function of DCs. Furthermore, we

Automated summary

Prostate cancer (PCa) is a solid malignancy with worse prognosis when there is a higher infiltration of T cells in the tumor microenvironment (TME). In this study, the focus was on dendritic cells (DCs), which are professional antigen-presenting cells. Tumor cells were found to stimulate the migration of immature DCs to the tumor site by inducing inflammatory chemokines. Various signaling pathways were up-regulated in DCs at the tumor location, while certain molecules on the surface of DCs decreased. The study also explored the communication between DCs and macrophages in the TME, identifying molecular pairs involved in the migration of DCs and disruption of their antigen-presenting function.