Mar 21, 2020

Impact of metastatic prostate cancer on human bone marrow

bioRxiv
Ninib BaryawnoPeter Kharchenko

Abstract

Cancer-related mortality due to solid tumor malignancies is overwhelmingly due to the development and progression of metastases. In advanced prostate cancer, metastases most often involve the bone1 and generally represent incurable disease. It remains unclear what aspects of the bone marrow microenvironment make it hospitable to metastatic dissemination. Similarly, the impact of the metastatic tumor on hematopoiesis and the marrow immune response is poorly understood. Here we take advantage of rare spinal cord decompression surgeries to profile marrow and metastatic tumors from men with advanced prostate cancer at single-cell resolution. We contrast the cellular composition and transcriptional states in matched samples of tumor and liquid bone marrow collected at adjacent vertebral body levels, as well as bone marrow of orthopedic patients without malignancy. Metastatic prostate cancer was associated with hematopoietic suppression and multifaceted immune distortion. There was exhaustion of specific T-cell subsets, appearance of inflammatory lymphocytes and macrophages, and alteration of cytokine profiles. The chemokine CCL20 was notably overexpressed by myeloid cells, as was its cognate CCR6 receptor on T-cells. This dual overe...Continue Reading

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Mentioned in this Paper

CCRL2 wt Allele
Malignant Neoplasms
Bone Marrow
Transcription, Genetic
Neoplasms
Mouse Model
Orthopedics
Chemokine CCL20
T-Lymphocyte Subsets
Immune Response

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