Tumor microenvironment and lymphoma pathogenesis 2012_RUAN 2012年淋巴瘤国际会议资料.pdf

Tumor Microenvironment and Lymphoma Pathogenesis Jia Ruan, M.D., Ph.D. Center for Lymphoma Myeloma Weill Cornell Medical College March 24, 2012 Tumor Microenvironment Tumor Cells Macrophages •VEGF-A PMNs •VEGF-C •Proteases •MMPs •Chemokines •Chemokines Mast cells ECM •VEGF-A •bFGF Vasculatures •MMPs •Endothelia •Pericytes Fibroblasts Adapted from Coussens LM J. Exp. Med. V193 P F23, 2001. Tumor Stromal Cells: Characteristics Functions Cell Origins: Locally derived vs. distantly recruited (bone marrow cells) Hematopoietic progenitors - immune / inflammatory cells Endothelial progenitors - endothelial cells Pericyte progenitors - pericytes Mesenchymal progenitors - fibroblasts, myofibroblasts and cells of various mesenchymal lineages Functions: Vascular cells - tumor angiogenesis Immune / inflammatory cells - regulate immune balance, promote tumor growth, influence angiogenic switch Fibroblasts / myofibroblasts - promote tumor growth, transform ECM, modulate angiogenesis Chemokines / growth factors - relay paracrine signaling between tumor and stroma (both local distant sites) Reviewed in Rafii S. Nat Rev Cancer 2002; 2:826; McAllister