On the dual roles and polarized phenotypes of neutrophils in tumor development and progression

Angiotensin converting enzyme inhibitors and angiotensin II receptor antagonist attenuate tumor growth via polarization of neutrophils toward an antitumor phenotype

“…Neutrophils are known to polarize into protumoral phenotype in tumor-bearing hosts 16,17 and most of these immunosuppressive neutrophils are found in the spleen and tumors. 1,15 Consistent with these findings, we found that splenic and intratumoral neutrophils from control tumorbearing mice showed significant differences in surface marker expression compared with those from naive mice. Splenic neutrophils from control tumor-bearing mice showed the decreased expression of CD16 (Fcg receptor III), CD55 (Decay-accelerating factor), CD88 (C5a receptor), CD120a/b (TNF receptor), CD256 (TNF ligand superfamily member 13), CD137 (CD137, a TNF receptor family member), CD101 (immunoglobulin superfamily member 2), CD80 (co-stimulating molecule), and the increased expression of CD43 (leukosialin) and CD98 (large neutral amino acid transporter).…”

“…1,2,11 In addition, recent studies indicate that myeloidderived suppressor cells (MDSCs) is responsible for immunosuppression in tumor-bearing hosts. 1,2,12 Among immunosuppressive immune cells, granulocytic-myeloid derived suppressor cells (GMDSCs) share distinct features of neutrophils, including surface markers (Ly6G and CD11b) and morphology (ring-shaped nucleus). G-MDSCs suppress the immune response in tumorbearing hosts by expressing high levels of arginase 1 and facilitate tumor progression, invasion and metastasis.…”

“…Due to their highly toxic arsenals, activated neutrophils can kill tumor cells, thereby playing an antitumor role in the host (reviewed in Piccard et al 1 …”

The Multifaceted Roles Neutrophils Play in the Tumor Microenvironment

“…While chronic inflammation may promote tumorigenesis [5,20], the tumor cells themselves also attract immune cells through the secretion of a wide range of chemokines such as IL-8 (CXCL8 in human/CXCL2 in mouse), CCL2 (MCP-1), CCL3 (MIP-1α), CCL5 (RANTES), CXCL6 (huGCP-2), and KC (CXCL1), and cytokines such as IL-1β, IL-6, TNFα, GM-CSF, and G-CSF, thereby inducing inflammation [21][22][23][24][25][26][27][28][29][30][31][32]. Cytokines from tumors may regulate tumor growth or modify the anti-tumor immune responses [33][34][35][36].…”

“…Unlike the situation in infection and inflammation where neutrophil mobilizing factors are secreted by endothelial cells and other stromal cells, in the context of cancer, neutrophil mobilizing factors are often secreted by the tumor cells themselves [22]. The most common neutrophil chemoattractants produced by tumors include IL-8 (CXCL8/CXCL2), MIP-1α (CCL3), huGCP-2 (CXCL6) and KC (CXCL1) [167][168][169][170][171].…”