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Updated: Jun 20, 2026

Transfer of Manipulated Tumor-associated Neutrophils into Tumor-Bearing Mice to Study their Angiogenic Potential In Vivo
08:19

Transfer of Manipulated Tumor-associated Neutrophils into Tumor-Bearing Mice to Study their Angiogenic Potential In Vivo

Published on: July 20, 2019

Polarization of tumor-associated neutrophil phenotype by TGF-beta: "N1" versus "N2" TAN

Zvi G Fridlender1, Jing Sun, Samuel Kim

  • 1Thoracic Oncology Research Laboratory, 1016B ARC, University of Pennsylvania, Philadelphia, PA 19104-6160, USA. fridlender@hadassah.org.il

Cancer Cell
|September 8, 2009
PubMed

Insights

Transforming growth factor-beta (TGF-β) blockade enhances antitumor immunity by reprogramming tumor-associated neutrophils (TANs) into a cytotoxic phenotype. This blockade promotes neutrophil infiltration and activation, crucial for effective cancer immunotherapy.

Area of Science:

  • Immunology
  • Cancer Biology
  • Tumor Microenvironment

Background:

  • Transforming growth factor-beta (TGF-β) plays a critical role in tumor growth and immune suppression.
  • TGF-β blockade has shown promise in slowing tumor progression by activating CD8(+) T cells and macrophages.

Purpose of the Study:

  • To investigate the role of TGF-β blockade in modulating neutrophil function within the tumor microenvironment.
  • To determine the impact of TGF-β-induced neutrophils on antitumor immunity and CD8(+) T cell activation.

Main Methods:

  • Analysis of neutrophil populations (CD11b(+)/Ly6G(+)) in tumors following TGF-β blockade.
  • Assessment of neutrophil phenotype, including segmentation, cytotoxicity, and cytokine expression.
  • Experimental depletion of neutrophils to evaluate their contribution to antitumor effects.
  • Measurement of CD8(+) T cell activation in response to TGF-β blockade and neutrophil modulation.

Main Results:

  • TGF-β blockade increases neutrophil-attracting chemokines, leading to an influx of hypersegmented, cytotoxic tumor-associated neutrophils (TANs).
  • These activated TANs express higher levels of proinflammatory cytokines.
  • Depletion of neutrophils abrogates the antitumor effects of TGF-β blockade and reduces CD8(+) T cell activation.
  • In control tumors, neutrophil depletion enhances antitumor activity and CD8(+) T cell activation.

Conclusions:

  • TGF-β in the tumor microenvironment promotes a protumorigenic neutrophil phenotype.
  • TGF-β blockade shifts TANs towards an antitumorigenic phenotype, enhancing their cytotoxic activity and proinflammatory cytokine production.
  • Neutrophils are critical mediators of TGF-β blockade's efficacy in cancer immunotherapy.

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