Polarization of Tumor-Associated Neutrophil Phenotype by TGF-β: “N1” versuss “N2”TAN

Fridlender Zvi G., et al. 2009. Cancer Cell. 16, 183-194

Speaker: Jhih-Sin Lu (陸致信)                                      Time: 14:00~15:00,Dec.2, 2009

Commentator: Dr. Bei-Chang Yang (楊倍昌老師)      Place: Room 601

Abstract:

Myeloid cell-mediated inflammation in tumor microenvironment is a critical event in tumorigenesis ¹. Although the polarization of tumor-associated macrophages (TAMs) has been well studied, the role of tumor-associated neutrophils (TANs) remained controversial. Previous studies showed that blockade of transforming growth factor-β (TGF-β) by SM16 in tumor bearing mice can reduce tumor size and induce CD11b⁺ cell infiltration ² that suggests neutrophils may have antitumor acitivity. However, other reports indicate that neutrophils promote tumor growth by secreting chemokines and facilitating angiogenesis ¹. In this paper, authors demonstrated that infiltrated CD11b⁺ cells in tumors after SM16 treatment were primarily neutrophils. In addition, tumor-associated neutrophils with SM16 treatment exhibited ‘higher immunostimulatory activity’ than those without SM16 treatment, characterized by hypersegmented nucleus and more mRNA expressions of chemokines. Thus, the authors proposed that tumor-associate neutrophils (N1 and N2, respectively) may play distinct roles in tumorigenesis. The authors found that in SM16-treated mice, tumor-associated neutrophils (N1) produced more reactive oxygen species and reduced tumor size. CD8⁺  T cell in those mice increased neutrophil infiltration which, in turns, enhanced CD8⁺ T cell activation. Taken together, the authors demonstrated that, depending on TGF-β signaling in tumor microenvironment, neutrophils exhibited either antitumor (N1) or protumor (N2) phenomenon which is similar to the polarization of TAMs.

References:

1.      Alberto Mantovani et al.2008 Cancer-related inflammation. Nature 454:436-444

2.      Kim, S. et al. 2008 Systemic blockade of transforming growth factor-beta signaling augments the efficacy of immunogene therapy. Cancer Res. 68, 10247–10256