Blood Journal
Leading the way in experimental and clinical research in hematology

Mesenchymal stromal cells orchestrate follicular lymphoma cell niche through the CCL2-dependent recruitment and polarization of monocytes

  1. Fabien Guilloton1,
  2. Gersende Caron1,2,
  3. Cédric Ménard1,2,
  4. Céline Pangault1,2,
  5. Patricia Amé-Thomas1,2,
  6. Joëlle Dulong1,
  7. John De Vos3,
  8. Delphine Rossille4,
  9. Catherine Henry2,
  10. Thierry Lamy1,5,
  11. Olivier Fouquet6,
  12. Thierry Fest1,2, and
  13. Karin Tarte1,2
  1. 1Inserm U917, Université Rennes 1, Etablissement Français du sang, Bretagne, France;
  2. 2Pôle Cellules & Tissus, Centre Hospitalier Universitaire (CHU) Pontchaillou, Rennes, France;
  3. 3Institut de Recherche en Biothérapie, Hôpital Saint-Eloi, CHU Montpellier, Montpellier, France;
  4. 4Inserm U936, Université de Rennes 1, Bretagne, France;
  5. 5Service d'Hématologie Clinique, CHU Pontchaillou, Rennes, France; and
  6. 6Service de Chirurgie Thoracique et Cardiovasculaire, CHU Pontchaillou, Rennes, France

Abstract

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 BM. In addition, mesenchymal stromal cells (MSCs) support in vitro FL B-cell survival, in particular after their engagement toward lymphoid differentiation. We show here that BM-MSCs obtained from patients with FL (FL-MSCs) display a specific gene expression profile compared with MSCs obtained from healthy age-matched donors (HD-MSCs). 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 the FL-cell niche, is up-regulated in HD-MSCs by coculture with malignant B cells, and is overexpressed by FL-MSCs, in agreement with their capacity to recruit monocytes more efficiently than HD-MSCs. Moreover, FL-MSCs and macrophages cooperate to sustain malignant B-cell growth, whereas FL-MSCs drive monocyte differentiation toward a proangiogenic and lipopolysaccharide-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.

  • Submitted August 3, 2011.
  • Accepted January 13, 2012.
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