Table 1.
List of diffusible mediators along with their cellular origin, potential impact on neutrophils and tumor progression, and the study models.
| Cancer Type | Source of diffusible mediators in the TME | Diffusible Mediators | Potential impact on neutrophils | Model | Ref |
|---|---|---|---|---|---|
| breast cancer | tumor-associated mesenchymal stromal cells | CXCL1, CXCL2, CXCL5 | increased migration to tumor site | mouse | (22) |
| γδ T cells at tumor site | IL-17 | increased migration to tumor site, change to pro-tumor phenotype, increased metastasis | mouse | (12) | |
| origin unclear | G-CSF (induced by IL-17) | ||||
| cancer cells | G-CSF | recruitment to metastatic sites | mouse | (23) | |
| cancer cells | chemokines active via CXCR2, TGF-β | increased migration | human (C) | (24) | |
| cancer cells | IL-6, CCL3 (induced by cathepsin c) | increased migration to tumor site, NET formation, ROS production; pro-metastasis (cathepsin c works via the PR3-IL-1β-NF-κB axis of neutrophils to upregulate secretion of IL-6 and CCL3) | mouse | (10) | |
| colorectal cancer | γδ T cells at tumor site | CXCL8 (IL-8), GM-CSF | increased migration | human (T) | (25) |
| IL-17A, GM-CSF | expansion of the PMN-MDSC population | ||||
| CXCL8 (IL-8), IL-17A, TNFα | extended survival | ||||
| platelets interacting with tumor cells in pre-metastatic niche | CXCL5, CXCL7 | increased recruitment to early pre-metastatic niche | mouse | (26) | |
| cancer cells | CXCL1 | increased recruitment to tumor site and tumor progression | mouse | (27) | |
| cancer cells | CXCL5 | increased recruitment to tumor site and increased metastasis | mouse | (28) | |
| origin unclear | TGF-β | increased recruitment to metastatic site | |||
| Th17 cells | CXCL8 (IL-8) | increased migration | human (T) | (29) | |
| hepato-cellular carcinoma | tumor-associated monocytes | CXCL2, CXCL8 | increased migration and extended survival | human (T) | (30) |
| cancer cells | CXCL5 | increased migration | mouse; human (C) | (31, 32) | |
| lung cancer | tumor-associated monocytes, macrophages, neutrophils, and DCs | CXCL1 | these migration-inducing chemokines are shown to have elevated levels of mRNA | mouse | (33) |
| TANs | CXCL2 | ||||
| cancer cells | CXCL5 | ||||
| melanoma | TANs | CXCL1, CXCL2 | increased migration to tumor site and angiogenesis | mouse | (34) |
| ovarian cancer | tumor cells | CXCL8 (most impact) and other chemokines active via CXCR2 | increased migration | human (T) | (35) |
| pancreatic cancer | cancer cells | CXCL5 | increased migration to tumor site via CXCR2 | mouse | (36) |
| stromal cells | CXCL2 | ||||
| PDAC tumors | GM-CSF, G-CSF | these migration-inducing chemokines are shown to have elevated levels of mRNA | human (T) | (37) | |
| neoplastic ductal cells | CXCL1, CXCL2, CXCL5, CXCL8 | human (T) | |||
| tumor cells | GM-CSF, G-CSF, CXCL1, CXCL2, CXCL5 | increased migration to tumor site via CXCR2 | mouse | ||
| thyroid cancer | cancer cells | chemokines active via CXCR1/2 | increased migration | human (C) | (38) |
| GM-CSF | increased survival |
The model type is specific for the experiments that detailed the impact on neutrophils. C, cell line; T, tissue.