Influence of the tumor microenvironment on FL

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Influence of the tumor microenvironment on FL Influence of the tumor microenvironment on FL. Tumor growth and survival are supported (green arrows) by follicular dendritic cells, follicular helper T cells (TFH), and M2-type tumor-associated macrophages (TAMs) through expression of various ligands and r... Influence of the tumor microenvironment on FL. Tumor growth and survival are supported (green arrows) by follicular dendritic cells, follicular helper T cells (TFH), and M2-type tumor-associated macrophages (TAMs) through expression of various ligands and receptors on the cell surface, including the FC receptor and mannose receptors that bind the FL BCR and stimulate BCR signaling. Secretion of various cytokines and chemokines also supports tumor growth by directly stimulating FL cells and by shaping the microenvironment into one that is more accommodating for FL, including secretion of interleukin-4 (IL-4) by TFH cells to skew TAM activation toward a tumor-supportive M2 phenotype and secretion of transforming growth factor β (TGF-β) by TAMs to promote T-helper cell differentiation toward regulatory T cells that inhibit (red arrows) antitumor cytotoxic T cells. ICOS, inducible T-cell costimulator. Brad S. Kahl, and David T. Yang Blood 2016;127:2055-2063 ©2016 by American Society of Hematology