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. 2021 Oct 13;9(10):e002873. doi: 10.1136/jitc-2021-002873

Table 3.

Pro-tumoral and anti-tumoral roles of cytokines and chemokines in primary and metastatic ovarian carcinoma

Histology Stage No of patients Method Impact Note Ref.
Primary lesion
IL-6 *EOC All 94 IHC Detrimental High IL-6 levels correlated with proliferation and invasivity of cancer cells 159
EOC All 221 IHC Detrimental High IL-6 levels correlated with tumor growth, high frequency of TAMs infiltrate, angiogenesis and poor disease outcome 157
HGSOC III, IV 53 IHC, IF Detrimental High IL-6 levels correlated with angiogenesis, increased infiltration of myeloid cells and poor disease outcome 156
  n.a. n.a. 25 IHC Detrimental High IL-6 levels correlated with disease progression 158
IL-8 HGSOC,
MOC,
EnOC		 All 44 RT-PCR, IHC Detrimental High IL-8 levels correlated with malignant transformation and poor disease outcome 164
IL-10 HGSOC III, IV 30 ELISA Detrimental High IL-10 levels correlated with M2-like TAMs polarization and poor prognosis 65
TGFβ EOC All 92 IHC, FC Detrimental High TGFB1 levels associated with CD8+ Treg induction and poor prognosis 66
HGSOC,
EnOC		 All 25 IHC, RT-PCR Detrimental High TGFβ levels associated with cancer cells proliferation and poor disease outcome 163
VEGF HGSOC III, IV 56 Microarray, IHC Detrimental High VEGF levels correlated with MDSC migration and poor prognosis 14
HGSOC,
MOC,
EnOC		 All 44 RT-PCR, IHC Detrimental High VEGF levels correlated with malignant transformation and poor prognosis 164
TNFα EOC III, IV 60 FC, ELISA,
RT-PCR		 Detrimental High TNF levels correlated with myeloid cells recruitment and tumor progression 165
HGSOC III, IV 53 IHC, IF Detrimental High TNF levels correlated with angiogenesis, increased infiltration of myeloid cells and poor disease outcome 156
IDO EOC All 60 IHC Detrimental High IDO levels correlated with impaired OS and PFS 78
CCL2 HGSOC,
MOC,
EnOC		 All 46 ELISA Detrimental High CCL2 levels correlated with TAMs recruitment and poor disease outcome 170
CCL5 n.a. All n.a. ELISA,
RT-PCR		 Beneficial High CCL5 levels associated with recruitment of effector CD8+ T cells and favorable disease outcome 133
CCL18 HGSOC, MOC All 59 RT-PCR,
IHC		 Detrimental High CCL18 levels correlated with metastatic spread and poor disease outcome 175
CCL22 EOC All 70 ELISA Detrimental High CCL22 levels associated with recruitment of TREG cells and poor disease outcome 54
CCL28 HGSOC III, IV 88 IHC Detrimental High CCL28 levels associated with recruitment of TREG cells and poor disease outcome 61
CXCL9, CXCL10 HGSOC III, IV 184 IHC Beneficial High CXCL9 and CXCL10 levels associated with recruitment of effector CD8+ T cells and favorable prognosis 70
CXCL12 HGSOC III, IV 53 IHC IF Detrimental High CXCL12 levels correlated with angiogenesis, increased infiltration of myeloid cells and poor disease outcome 156
HGSOC, EnOC All 44 IHC Detrimental High CXCR4 expression correlated with cancer cells proligeration and poor disease outcome 173
CXCL13 HGSOC All 264 IHC, IF Beneficial High CXCL13 levels correlated with recruitment of CXCR5+CD8+ T cells in TLS and favorable disease outcome 190
CXCL16 HGSOC All 60 IHC Detrimental High CXCR6 expression correlated with metastatic spread and poor disease outcome 169
CXCL17 HGSOC n.a. n.a. RT-PCR Beneficial High CXCL17 levels associated with recruitment of DCs and favorable disease outcome 74
Metastatic lesion
IL-6 EOC All 70 Luminex Detrimental High IL-6 levels in malignant ascites correlated with chemo-resistance and poor PFS 168
EOC All 31 ELISA Detrimental High IL-6 and IL-10 levels correlated with accumulation of CD14+HLA-DR-MDSCs in malignant ascites and poor disease outcome 111
HGSOC III, IV 30 ELISA Detrimental High IL-6 levels correlated with accumulation of CD163+CD68+ M2-like TAMs in malignant ascites and poor disease outcome 65
IL-10 HGSOC III, IV 30 ELISA Detrimental High IL-10 levels correlated with M2-like TAMs polarization and poor prognosis 65
VEGF HGSOC III, IV 56 Microarray IHC Detrimental High VEGF levels correlated with accumulation of MDSCs and poor disease outcome 14
TNFα EOC All 70 Luminex Detrimental High TNFα levels in malignant ascites correlated with chemoresistance and poor PFS 168
CCL18 HGSOC III, IV 53 RT-PCR,
ELISA, WB		 Detrimental High CCL18 levels correlated with cancer cells proliferation and metastatic spread 174
CCL22 n.a. All 70 ELISA Detrimental High CCL22 levels correlated with recruitment of TREG cells and poor disease outcome 54
CXCL12 EOC III, IV n.a. ELISA, FC Detrimental High CXCL12 levels correlated with accumulation of MDSCs in malignant ascites and poor disease outcome 113

*Encompassing all EOC histological subtypes

CCL18, C-C motif chemokine ligand 18; CXCL12, C-X-C motif chemokine ligand 12; DC, dendritic cell; EnOC, endometroid ovarian cancer; EOC, epithelial ovarian carcinoma; FC, flow cytometry; HGSOC, high-grade serous ovarian carcinoma; IDO, indoleamine 2,3-dioxygenase; IF, immunofluorescence; IHC, immunohistochemistry; IL6, interleukin 6; MDSC, myeloid-derived suppressor cell; MOC, mucinous ovarian cancer; n.a., not available; OS, overall survival; PFS, progression-free survival; TAM, tumor associated macrophage; TGFB, transforming growth factor; TLS, tertiary lymphoid structure; TNFα, tumor necrosis factor alpha; TREG, regulatory T cell; VEGF, vascular endothelial growth factor; WB, western blotting.