Newswire (Published: Wednesday, April 22, 2020, Received: Wednesday, April 22, 2020, 6:06:55 PM CDT)
Word Count: 300
2020 APR 22 (NewsRx) -- By a
“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 overexpression was associated with repressed immune responses. We used a syngeneic mouse model of bone-metastatic prostate cancer to explore this observation, and demonstrated that disruption of the CCL20-CCR6 axis resulted in significant prolongation of survival. Overall, comparative high-resolution analysis of bone marrow reveals distinct alterations associated with prostate cancer bone metastases that may be amenable to therapeutic targeting with the goal of altering cancer progression.”
This preprint may not have been peer-reviewed. For more information on this research see: http://biorxiv.org/content/10.1101/2020.03.19.998658v1
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