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

Adib Miraki Feriz; Arezou Khosrojerdi; Mohammad Lotfollahi; Neusha Shamsaki; Mohammad GhasemiGol; Edris HosseiniGol; Mohammad Fereidouni; Mohammad Hossein Rohban; Ahmad Reza Sebzari; Samira Saghafi; Patrizia Leone; Nicola Silvestris; Hossein Safarpour; Vito Racanelli

doi:10.1016/j.heliyon.2023.e15694

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

Heliyon. 2023 Apr 23;9(5):e15694. doi: 10.1016/j.heliyon.2023.e15694. eCollection 2023 May.

Authors

Adib Miraki Feriz^{1

2}, Arezou Khosrojerdi², Mohammad Lotfollahi^{3

4}, Neusha Shamsaki¹, Mohammad GhasemiGol⁵, Edris HosseiniGol⁶, Mohammad Fereidouni², Mohammad Hossein Rohban⁷, Ahmad Reza Sebzari⁸, Samira Saghafi¹, Patrizia Leone⁹, Nicola Silvestris¹⁰, Hossein Safarpour², Vito Racanelli⁹

Affiliations

¹ Birjand University of Medical Sciences (BUMS), Birjand, Iran.
² Cellular and Molecular Research Center, BUMS, Birjand, Iran.
³ Computational Health Center, Helmholtz Munich, Germany.
⁴ Wellcome Sanger Institute, Cambridge, UK.
⁵ College of Engineering & Mines, University of North Dakota, North Dakota, USA.
⁶ Department of Computer Engineering, University of Birjand, Birjand, Iran.
⁷ Department of Computer Engineering, Sharif University of Technology, Tehran, Iran.
⁸ Radiation Oncology, Clinical Research Development Unit (CRDU), ValiAsr Hospital, BUMS, Birjand, Iran.
⁹ Department of Biomedical Sciences and Human Oncology, University of Bari "Aldo Moro", Bari, Italy.
¹⁰ Medical Oncology Unit, Department of Human Pathology "G. Barresi", University of Messina, Messina, Italy.

Abstract

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-α/NF-κB, 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 T_regs. 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 presented new therapeutic targets by the construction of a gene co-expression network. These data increase our knowledge of the heterogeneity and the role of DCs in PCa TME.

Keywords: Dendritic cells; Immunotherapy; Prostate cancer; Single-cell RNA sequencing; Tumor microenvironment.