Mesenchymal stromal cells orchestrate follicular lymphoma cell niche through the CCL2-dependent recruitment and polarization of monocytes
Cette étude met en évidence le rôle joué par des cellules stromales mésenchymateuses dans la croissance tumorale des lymphomes folliculaires
Accumulating evidence indicates that infiltrating stromal cells contribute directly and indirectly to tumor growth in a wide range of cancers. In follicular lymphoma (FL), malignant B cells are found admixed with heterogeneous lymphoid-like stromal cells within invaded lymph nodes and bone marrow (BM). In addition, mesenchymal stromal cells (MSC) support in vitro FL B-cell survival, in particular after their engagement towards lymphoid differentiation. We show here that BM-MSC obtained from FL patients (FL-MSC) display a specific gene expression profile compared to MSC obtained from healthy age-matched donors (HD-MSC). This FL-MSC signature is significantly enriched for genes associated with a lymphoid-like commitment. Interestingly, CCL2 could be detected at a high level within FL cell niche, is upregulated in HD-MSC by coculture with malignant B cells, and is overexpressed by FL-MSC, in agreement with their capacity to recruit monocytes more efficiently than HD-MSC. Moreover, FL-MSC and macrophages cooperate to sustain malignant B-cell growth whereas FL-MSC drive monocyte differentiation towards a proangiogenic and LPS-unresponsive phenotype close to that of tumor-associated macrophages. Altogether, these results highlight the complex role of FL stromal cells that promote direct tumor B-cell growth and orchestrate FL cell niche, thus emerging as a potential therapeutic target in this disease.