Table 2.

Cytokine function

Cytokine	Function	Predicted Impact on Patient Survival	Reference
4-1BB/TNFRSF9/CD137	promotes the movement of monocytes/macrophages to the tumor microenvironment and promotes metastasis of breast cancer to bone	negative	[41]
BAFF/BLyS/TNFSF13B	increases stemness in epithelial breast cancer cells which promotes metastasis	negative	[23]
C-Reactive Protein/CRP	inflammatory protein that is produced in response to IL-6, elevated levels are associated with more aggressive tumors	negative	[42]
CCL2/JE/MCP-1	recruits and activates tumor-related macrophages that promote tumor growth and angiogenesis	negative	[32]
CCL20/MIP-3 alpha	attracts CCR6 which allows breast cancer cells to break through the extracellular matrix resulting in angiogenesis and metastasis	negative	[43]
CCL22/MDC	associated with accumulation of tumor-associated macrophages	negative	[32,44]
CCL3/MIP-1 alpha	promotes breast cancer cell migration	negative	[32]
CCL4/MIP-1 beta	high expression promotes tumor development	negative	[32]
CCL5/RANTES	promotes growth, angiogenesis, and metastasis	negative	[20]
CCL7/MCP-3/MARC	promotes breast cancer cell proliferation and is involved in metastasis to bone	negative	[45]
CCL8/MCP-2	recruits and activates tumor-related macrophages that promote tumor growth and angiogenesis	negative	[46]
Chitinase 3-like 1	induces pro-angiogenic/pro-tumorigenic factors	negative	[14]
			general role in cancer
CXCL10/IP-10/CRG-2	inhibits tumor growth by inducing Granzyme B, mediates the NF-kB pathway	not determined	[20]
CXCL11/I-TAC	induces cancer cell migration	negative	[22]
			general role in cancer
CXCL13/BLC/BCA-1	increases cell proliferation, levels of IL-1, TNF, and TGF; decreases apoptosis	negative	[20]
CXCL14/BRAK	inhibits tumor angiogenesis, proliferation, and invasion of cancer cells	positive	[20]
CXCL5/ENA-78	promotes tumor angiogenesis	negative	[20]
CXCL9/MIG	inhibits chemotaxis to endothelial cells	positive	[20]
Fas Ligand/TNFSF6	induces apoptosis; cancer cells that are able to escape the effects of the immune system can use this cytokine to mediate their survival	not determined	[47]
			general role in cancer
Fas/TNFRSF6/CD95	involved in eliminating tumor-infiltrating immune cells and tissue destruction	negative	[48]
Ferritin	downregulation is associated with increased apoptosis	positive	[49]
			general role in cancer
G-CSF	high levels can induce the formation of neutrophilic extracellular traps which promote breast cancer cell migration	negative	[50]
GM-CSF	inactivates VEGF and blocks angiogenesis	positive	[51]
Granzyme B	used by cytotoxic T lymphocytes and natural killer cells to induce cell death	positive	[52]
			general role in cancer
IFN-alpha	induces the activation of the STAT1 pathway	negative	[53,54]
			general role in cancer
IFN-β	can induce autophagy in response to IFN-β treatment	not determined	[15]
IFN-gamma	inhibits cell proliferation	positive	[55]
IFN-gamma R1/CD119	inhibits cell proliferation	positive	[55]
IL-1 beta/IL-1F2	makes the tumor more aggressive and invasive	not determined	[21]
IL-10	high levels are associated with metastasis	not determined	[21]
IL-12/IL-23 p40	promotes inflammation and angiogenesis	negative	[56]
IL-15	increases and activates natural killer cells	not determined	[57]
IL-17/IL-17A	inhibits apoptosis through NF-kB activation, promotes angiogenesis, makes cells more aggressive	negative	[29,58]
IL-2	high levels associated with more aggressive tumors	not determined	[21]
IL-21	promotes proliferation and invasiveness of breast cancer cells	negative	[21]
IL-4	induces apoptosis in breast cancer cells by producing macrophages and eosinophils	positive	[59]
IL-6	decreases responsiveness to endocrine and chemotherapy	negative	[18]
IL-7	promotes survival and growth of breast cancer cells	negative	[21]
IL-8/CXCL8	low levels are related with lack of hormone receptors and metastasis	negative	[19]
M-CSF	promotes metastasis	negative	[51]
PD-L1/B7-H1	associated with higher tumor grade and increased infiltration of T regulatory cells	negative	[60]
Prolactin	plays a role in tumorigenesis	negative	[61]
TNF-alpha	pro-tumorigenic and contributes to drug resistance development	negative	[62]
TRAIL R2/TNFRSF10B	low levels of membrane-bound associated with metastasis, migration, and invasion of cancer cells	negative	[63]
			general role in cancer
TRAIL R3/TNFRSF10C	high levels of membrane-bound associated with metastasis	negative	[64]
TRAIL/TNFSF10	selectively triggers cancer cell death	positive	[17]
			general role in cancer
TRANCE/TNFSF11/RANKL	induced by progesterone resulting in the proliferation of mammary progenitor cells	not determined	[65]
TREM-1	triggers amplification of inflammatory responses in the tumor	not determined	[66]
			role in lung cancer
VEGF	high levels are associated with tumors that have large sizes, high histological grade	negative	[67]
VEGFR3/Flt-4	promotes breast cancer cell proliferation and survival	negative	[68]

A panel of 52 cytokines that mediate different pro- or anti- cancer effects were evaluated in the MCF7 and HCT116 cell lines. The function and impact on survival of these cytokines in BC patients based on existing literature is outlined here.