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Feriz, A.M.* ; Khosrojerdi, A.* ; Lotfollahi, M. ; Shamsaki, N.* ; GhasemiGol, M.* ; HosseiniGol, E.* ; Fereidouni, M.* ; Rohban, M.H.* ; Sebzari, A.R.* ; Saghafi, S.* ; Leone, P.* ; Silvestris, N.* ; Safarpour, H.* ; Racanelli, V.*

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

Heliyon 9:e15694 (2023)
Verlagsversion DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
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 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 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.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Dendritic Cells ; Immunotherapy ; Prostate Cancer ; Single-cell Rna Sequencing ; Tumor Microenvironment
Sprache englisch
Veröffentlichungsjahr 2023
HGF-Berichtsjahr 2023
ISSN (print) / ISBN 2405-8440
e-ISSN 2405-8440
Zeitschrift Heliyon
Quellenangaben Band: 9, Heft: 5, Seiten: , Artikelnummer: e15694 Supplement: ,
Verlag Elsevier
Verlagsort London [u.a.]
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Computational Biology (ICB)
POF Topic(s) 30205 - Bioengineering and Digital Health
Forschungsfeld(er) Enabling and Novel Technologies
PSP-Element(e) G-503800-001
DOI 10.1016/j.heliyon.2023.e15694
PubMed ID 37144199
Erfassungsdatum 2023-10-06
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