RRC ID 69789
Author Shibuya T, Kamiyama A, Sawada H, Kikuchi K, Maruyama M, Sawado R, Ikeda N, Asano K, Kurotaki D, Tamura T, Yoneda A, Imada K, Satoh T, Akira S, Tanaka M, Yotsumoto S.
Title Immunoregulatory Monocyte Subset Promotes Metastasis Associated With Therapeutic Intervention for Primary Tumor.
Journal Front Immunol
Abstract Systemic and local inflammation associated with therapeutic intervention of primary tumor occasionally promotes metastatic recurrence in mouse and human. However, it remains unclear what types of immune cells are involved in this process. Here, we found that the tissue-repair-promoting Ym1+Ly6Chi monocyte subset expanded as a result of systemic and local inflammation induced by intravenous injection of lipopolysaccharide or resection of primary tumor and promoted lung metastasis originating from circulating tumor cells (CTCs). Deletion of this subset suppressed metastasis induced by the inflammation. Furthermore, transfer of Ym1+Ly6Chi monocytes into naïve mice promoted lung metastasis in the mice. Ym1+Ly6Chi monocytes highly expressed matrix metalloproteinase-9 (MMP-9) and CXCR4. MMP-9 inhibitor and CXCR4 antagonist decreased Ym1+Ly6Chi-monocyte-promoted lung metastasis. These findings indicate that Ym1+Ly6Chi monocytes are therapeutic target cells for metastasis originating from CTCs associated with systemic and local inflammation. In addition, these findings provide a novel predictive cellular biomarker for metastatic recurrence after intervention for primary tumor.
Volume 12
Pages 663115
Published 2021-1-1
DOI 10.3389/fimmu.2021.663115
PMID 34163472
PMC PMC8215602
MeSH Animals Antigens, Ly / metabolism Biomarkers, Tumor Cell Line, Tumor Cell Plasticity / immunology* Disease Management Disease Models, Animal Disease Susceptibility Gene Expression Regulation, Neoplastic Immunomodulation* / genetics Immunophenotyping Inflammation / immunology Inflammation / metabolism Inflammation / pathology Lung Neoplasms / pathology Lung Neoplasms / secondary Matrix Metalloproteinase 9 / genetics Matrix Metalloproteinase 9 / metabolism Melanoma, Experimental Mice Mice, Transgenic Monocytes / immunology* Monocytes / metabolism* Neoplasm Metastasis Neoplasm Staging Neoplasms / etiology* Neoplasms / metabolism Neoplasms / pathology* Neoplasms / therapy Receptors, CXCR4 / metabolism
IF 5.085
Human and Animal Cells B16F10(RCB2630)