CD8+ T cells from experimental in situ breast carcinoma interfere with bone homeostasis.

摘要: Abstract Before bone colonization, immune cells primed by breast primary tumor actively modify the microenvironment, disturbing complex and tightly homeostatic signaling network regulated osteoblasts osteoclasts. Indeed, we have shown that RANKL+ CD4+ T specific for 4T1 mammary carcinoma cell line, arrive at marrow (BM) before metastatic set pre-metastatic niche. In absence of RANKL expressed cells, there is no osteolytic disease metastases are blocked. Adding to role recently demonstrated dendritic (DCs) provide a positive feedback loop profile induced tumor. this setting, DCs able differentiate into potent resorbing osteoclast-like keeping their antigen-presenting (APC) properties maintain Th17 activities, via IL-23 expression. Here show 67NR non-metastatic sibling induce an increase in trabecular mass on day 11 post-tumor implant. This observation was associated with expansion osteoblastic lineage accompanied reduction osteoclasts numbers. Moreover, derived CD8+ from tumor-bearing mice, express anti-osteoclastogenic cytokine milieu enriched IFN-γ, IL-10 producing low levels RANKL. The frequency BM FoxP3+ regulatory known as suppressors osteoclastogenesis both vitro vivo, also increased such animals. capable suppress tumor-specific phenotype vivo strongly inhibited establishment, restoring volume. We concluded 67NR+ phenotypes, either contributing homeostasis and/or control disease, interfere activities inside BM. Our study highlights opposing roles subverted subtypes directing cancer progression establishment. For tumors, regarding remodeling has never been addressed before. As far know, first description situ can distant sites. case showed here, modification site disfavors niche formation.