[PDF][PDF] Polarization of tumor-associated neutrophil phenotype by TGF-β:“N1” versus “N2” TAN

ZG Fridlender, J Sun, S Kim, V Kapoor, G Cheng… - Cancer cell, 2009 - cell.com
ZG Fridlender, J Sun, S Kim, V Kapoor, G Cheng, L Ling, GS Worthen, SM Albelda
Cancer cell, 2009cell.com
TGF-β blockade significantly slows tumor growth through many mechanisms, including
activation of CD8+ T cells and macrophages. Here, we show that TGF-β blockade also
increases neutrophil-attracting chemokines, resulting in an influx of CD11b+/Ly6G+ tumor-
associated neutrophils (TANs) that are hypersegmented, more cytotoxic to tumor cells, and
express higher levels of proinflammatory cytokines. Accordingly, following TGF-β blockade,
depletion of these neutrophils significantly blunts antitumor effects of treatment and reduces …
Summary
TGF-β blockade significantly slows tumor growth through many mechanisms, including activation of CD8+ T cells and macrophages. Here, we show that TGF-β blockade also increases neutrophil-attracting chemokines, resulting in an influx of CD11b+/Ly6G+ tumor-associated neutrophils (TANs) that are hypersegmented, more cytotoxic to tumor cells, and express higher levels of proinflammatory cytokines. Accordingly, following TGF-β blockade, depletion of these neutrophils significantly blunts antitumor effects of treatment and reduces CD8+ T cell activation. In contrast, in control tumors, neutrophil depletion decreases tumor growth and results in more activated CD8+ T cells intratumorally. Together, these data suggest that TGF-β within the tumor microenvironment induces a population of TAN with a protumor phenotype. TGF-β blockade results in the recruitment and activation of TANs with an antitumor phenotype.
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