Interleukin-6 receptor and its ligand interleukin-6 are opposite markers for survival and infiltration with mature myeloid cells in ovarian cancer

  title={Interleukin-6 receptor and its ligand interleukin-6 are opposite markers for survival and infiltration with mature myeloid cells in ovarian cancer},
  author={Mca Wouters and Em Dijkgraaf and M L Kuijjer and E. S. Jordanova and H. Hollema and M. J. P. Welters and Jjm van der Hoeven and Toos Daemen and J. R. Kroep and H W Nijman and S.H. van der Burg},
An increased level of interleukin-6 (IL-6) in epithelial ovarian cancer (EOC) is correlated with a worse prognosis. IL-6 stimulates tumor-growth and inflammation. We investigated the intricate interaction between the IL-6 signaling pathway and tumor-infiltrating myeloid cells (TIMs) to determine their prognostic impact in EOC. 160 EOC samples were analyzed for the expression of IL-6, its receptor (IL-6R) and downstream signaling via pSTAT3 by immunohistochemistry. Triple color… 

High mRNA expression level of IL-6R was associated with better prognosis for patients with ovarian cancer: a pooled meta-analysis

Results showed that mRNA levels of IL-6R in ovarian cancer was positively associated with better prognosis and sensitivity to chemotherapy and can potentially be used as a prognostic marker for this cancer.

IL-6/IL-6R pathway is a therapeutic target in chemoresistant ovarian cancer

It is suggested that blockade of the IL-6 signaling pathway with anti-IL-6 receptor antibody tocilizumab might resensitize the chemoresistant cells to the current chemotherapeutic agents.

Ascites-derived IL-6 and IL-10 synergistically expand CD14+HLA-DR-/low myeloid-derived suppressor cells in ovarian cancer patients

It is demonstrated that abundant M-MDSC are present in both periphery and ascites of OC patients whose accumulation and suppressive activity is critically attributable to ascites-derived IL-6 and IL-10 and their downstream STAT3 signal, thus providing a potentially novel therapeutic option by locally targeting MDSC to improve antitumor efficacy.

CD163+ cytokine-producing cDC2 stimulate intratumoral type 1 T cell responses in HPV16-induced oropharyngeal cancer

An important role is suggested for intratumoral CD163+ cDC2 in stimulating tumor-infiltrating T cells to exert their antitumor effects.

The blood mMDSC to DC ratio is a sensitive and easy to assess independent predictive factor for epithelial ovarian cancer survival

The baseline blood mMDSC to DC ratio is a robust, independent and easy to analyze predictive factor for EOC survival, and may assist patient selection for immunotherapy.

Interleukin-6: a molecule with complex biological impact in cancer.

The pharmacological treatment impairing IL-6 signalling represents a potential mechanism of anti-tumour therapy targeting cancer growth, metastatic spread, metabolic deterioration and terminal cachexia in patients.

Paeonol Suppresses Proliferation and Motility of Non-Small-Cell Lung Cancer Cells by Disrupting STAT3/NF-κB Signaling

Paeonol potently inhibited NSCLC cell growth, migration and invasion associated with disruption of STAT3 and NF-κB pathways, suggesting that it could be a promising anti-metastatic candidate for tumor chemotherapy.

Immune‐suppressive effects of interleukin‐6 on T‐cell‐mediated anti‐tumor immunity

The IL‐6‐targeting approach is of value as a promising strategy for desensitization and prevention of immune‐suppressive effects, and should be an effective treatment when combined with current immunotherapies.



Interleukin-6/interleukin-6 receptor pathway as a new therapy target in epithelial ovarian cancer.

The role of the interleukin-6 (IL-6) in chemoresistance and suppression of tumor immunity in ovarian cancer is reviewed and the rationale for modulating the IL-6/ IL-7R induced pathway is provided as a potential new target for the treatment of ovarian cancer.

Targeted anti-interleukin-6 monoclonal antibody therapy for cancer: a review of the rationale and clinical evidence.

In six clinical studies of mAbs to IL-6 with BE-8 or CNTO 328 in patients with multiple myeloma, renal cell carcinoma, and B-lymphoproliferative disorders, anti-IL-6 mAb treatment decreased C-reactive protein levels in all patients, and the antibodies were well tolerated, and no serious adverse effects were observed in the vast majority of studies.

Mixed-polarization phenotype of ascites-associated macrophages in human ovarian carcinoma: Correlation of CD163 expression, cytokine levels and early relapse

A subgroup of patients with high CD163 expression, high IL‐6 and/or IL‐10 levels and poor clinical outcome is defined, which is defined as a sub group of patients without a clear inverse association with RFS, and with a mixed‐polarization phenotype unrelated to the M1/M2 classification.

Tumor‐infiltrating CD14‐positive myeloid cells and CD8‐positive T‐cells prolong survival in patients with cervical carcinoma

Results indicate that reinforcement and activation of the intratumoral M1 macrophages may form an attractive immunotherapeutic option in CxCa.

Interleukin-6 as a Therapeutic Target in Human Ovarian Cancer

Purpose: We investigated whether inhibition of interleukin 6 (IL-6) has therapeutic activity in ovarian cancer via abrogation of a tumor-promoting cytokine network. Experimental Design: We combined