Single-Cell RNA Sequencing Identifies CCR6-Driven Immune Landscape Changes in RM1 Prostate Cancer Bone Metastasis.

Area of Science:

• Immunology
• Oncology
• Genomics

Background:

• Prostate cancer frequently metastasizes to bone, creating an immunosuppressive microenvironment that promotes tumor growth.
• The RM1 (Ras/Myc) mouse model is crucial for studying prostate tumor and bone marrow immune interactions.

Purpose of the Study:

• To investigate the impact of CCR6 deficiency on immune cell communication in the bone marrow of a mouse model of prostate cancer bone metastasis.
• To compare immune responses between wild-type and CCR6 knockout mice with RM1 prostate cancer bone metastasis.

Main Methods:

• Utilized single-cell RNA sequencing to analyze immune cell communication in bone marrow from RM1 prostate cancer bone metastasis models.
• Compared immune responses between wild-type and CCR6 knockout (CCR6ko) mice injected with RM1-BoM3 cells.

Main Results:

• CCR6 deficiency altered immune cell signaling, including macrophages, regulatory T cells, and myeloid-derived suppressor cells.
• Differential gene expression revealed immune suppression pathways (JUN, JUNB, FOSB) and altered cell-cell communication (CCL, TGFb, MIF, CXCL).
• Identified increased tumor-infiltrating monocytic cells, M2 macrophages, and NKT-like CD8 cells in RM1 tumors; upregulated IL-17 signaling and osteoclast differentiation pathways.

Conclusions:

• Targeting CCR6 could enhance immunotherapy efficacy in prostate cancer bone metastasis by modulating the immune microenvironment.
• Conserved immune interactions were observed in human castration-resistant prostate cancer (CRPC) bone metastasis datasets, suggesting therapeutic potential.