High Serum Levels of Soluble IL-2 Receptor, Cytokines, and C Reactive Protein Correlate with Impairment of T Cell Response in Patients with Advanced Epithelial Ovarian Cancer

Abstract This study was undertaken to determine if advanced epithelial ovarian cancer was associated with increased serum and ascitic levels of soluble interleukin-2 receptor alpha (sIL-2R alpha). Serum and ascitic fluid samples from 23 ovarian cancer patients were analyzed for sIL-2R alpha using an enzyme-linked immunosorbent assay and compared with the serum and peritoneal levels in 18 normal females. The samples were analyzed for CA-125 levels using a radioimmunoassay and the total protein was also measured. Normal individuals had low serum levels of sIL-2R alpha (367.5 +/- 44.6 U/mL), with similar levels of sIL-2R alpha in the normal peritoneal fluid (438.6 +/- 48.8 U/mL). In contrast, the serum and ascitic fluid levels in ovarian cancer patients were significantly higher (746.7 +/- 82.9 U/mL, P = .0006; 2,656.7 +/- 373.7 U/mL, P = .00002, respectively). The results for sIL-2R alpha were also significant when the levels were expressed per milligram of total protein. More importantly, in almost every ovarian cancer patient the ascitic sIL-2R alpha level far exceeded the serum level, a pattern also observed for CA-125. There was no correlation between the serum and ascitic sIL-2R alpha levels, or between the serum and ascitic CA-125 levels. Although the serum levels of sIL-2R alpha and CA-125 were elevated in the same patient, overall there was no correlation between the serum sIL-2R alpha and serum CA-125 levels, either when the levels were expressed in absolute units or per milligram of total protein. Similarly, there was no correlation between sIL-2R alpha and CA-125 levels in individual ascitic samples. While CA-125 levels may reflect an independent index of tumor burden, these results suggest that selective accumulation of sIL-2R alpha in the ascites may be one of the factors associated with the known nonresponsiveness of the infiltrating lymphocytes against ovarian carcinoma cells.

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High serum levels of C-reactive protein (CRP) predict beneficial decrease of visceral fat in obese females after sleeve gastrectomy

Nutrition Metabolism and Cardiovascular Diseases ◽

10.1016/j.numecd.2018.01.014 ◽

2018 ◽

Vol 28 (5) ◽

pp. 494-500 ◽

Cited By ~ 16

Author(s):

F. Carbone ◽

E. Nulli Migliola ◽

A. Bonaventura ◽

A. Vecchié ◽

S. De Vuono ◽

...

Keyword(s):

Sleeve Gastrectomy ◽

Visceral Fat ◽

Serum Levels ◽

High Serum ◽

C Reactive Protein ◽

Reactive Protein

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Determinants of response to checkpoint inhibition in ovarian cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.e17538 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. e17538-e17538

Author(s):

Andrea Leigh Buras ◽

Alexandra Martin ◽

Jun Min Zhou ◽

David C Boulware ◽

Jose Conejo-Garcia ◽

...

Keyword(s):

Ovarian Cancer ◽

Overall Survival ◽

T Cell ◽

Cell Response ◽

Elispot Assay ◽

Checkpoint Inhibitors ◽

T Cell Response ◽

Post Treatment ◽

Combination Methods ◽

Mixed Response

e17538 Background: Despite evidence that ovarian cancer (OC) is an immunogenic disease, single-agent checkpoint inhibitors have shown limited response. A clinical trial was conducted evaluating dose-dense paclitaxel and pembrolizumab in platinum-resistant OC. Our aim was to evaluate for biomarkers of response to this combination. Methods: Immunohistochemistry was performed to identify PD–L1 and tumor infiltrating lymphocytes (TIL) in pretreatment formalin fixed paraffin embedded tissue. We performed flow cytometry on matched blood to identify presence of immunosuppressive myeloid-derived suppressor cells (MDSCs) in circulation. We performed T-cell receptor (TCR) sequencing on tumor and matched blood to evaluate whether an oligoclonal or polyclonal immune response would be associated with outcomes. On selected patients we assessed peripheral T-cell responses to treatment using an interferon-ɣ enzyme-linked immunospot (IFN-ɣ ELISpot) assay between excellent and poor responders. Cox proportional hazards model was used to estimate hazards ratios (HR) for response in relation to each biomarker. Kaplan-Meier analysis and log-rank test were used to evaluate associations between progression free survival (PFS), overall survival (OS) and each biomarker. Results: Analysis was limited to 34 patients with tumor available and one RECIST response evaluation. Odds of response trended higher (OR = 4.1) in patients with PD-L1 (+) than patients with PD-L1 (-) tumors (p = 0.061). When restricting analysis to best response of CR/PR versus PD, the odds was 13.0 (p = 0.041). Patients with PD-L1(+) tumors had a HR for progression 0.56 (0.26-1.22; p = 0.144). Presence of TILs was classified as 0-3 (0-1 low, 2-3 high). High TIL presence was not associated with response, but was associated with improved OS and trend toward improved PFS; HR 0.29 (0.09-0.90, p = 0.022) and HR 0.47 (0.21-1.05, p = 0.06). Pre- and post-treatment levels of MDSCs were not associated with response or survival, though a trend was noted; a one unit increase in pretreatment MDSCs leads to 5% decrease in the odds of being responder. Immunoseq analysis of TCR repertoire pre- and post-treatment suggested that in increase in productive clonality was associated with increased odds of being a responder; this was not statistically significant. Notably, IFN-ɣ ELISpot assay demonstrated a significant T-cell response against neoantigens post-treatment in patients who had a partial response and long overall survival. Post treatment T-cell response showed a significantly mixed response to neoantigens in the patient analyzed who had progressive disease. Conclusions: Finding biomarkers predicting benefit from checkpoint inhibitors has been challenging. Though inconclusive, these data suggest biomarkers that may be associated with this combination. T-cell response to neoantigens in patients with response to treatment suggests neoantigens as a potential target for therapeutic direction.

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Prognostic evaluation of preoperative serum C-reactive protein concentration in patients with epithelial ovarian cancer

Experimental and Therapeutic Medicine ◽

10.3892/etm.2015.2350 ◽

2015 ◽

Vol 9 (5) ◽

pp. 2003-2007 ◽

Cited By ~ 10

Author(s):

YAPING LU ◽

SEN HUANG ◽

PING LI ◽

BINGYU CHEN ◽

WEILING LIU ◽

...

Keyword(s):

Ovarian Cancer ◽

Epithelial Ovarian Cancer ◽

Protein Concentration ◽

C Reactive Protein ◽

Prognostic Evaluation ◽

Reactive Protein ◽

Preoperative Serum

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High serum and ascitic soluble interleukin-2 receptor alpha levels in advanced epithelial ovarian cancer [see comments]

Blood ◽

10.1182/blood.v81.2.424.bloodjournal812424 ◽

1993 ◽

Vol 81 (2) ◽

pp. 424-429 ◽

Cited By ~ 1

Author(s):

DP Barton ◽

DK Blanchard ◽

B Michelini-Norris ◽

SV Nicosia ◽

D Cavanagh ◽

...

Keyword(s):

Ovarian Cancer ◽

Epithelial Ovarian Cancer ◽

Cancer Patients ◽

Ascitic Fluid ◽

Total Protein ◽

Interleukin 2 ◽

Serum Levels ◽

Ca 125 ◽

Soluble Interleukin 2 Receptor ◽

Advanced Epithelial Ovarian Cancer

This study was undertaken to determine if advanced epithelial ovarian cancer was associated with increased serum and ascitic levels of soluble interleukin-2 receptor alpha (sIL-2R alpha). Serum and ascitic fluid samples from 23 ovarian cancer patients were analyzed for sIL-2R alpha using an enzyme-linked immunosorbent assay and compared with the serum and peritoneal levels in 18 normal females. The samples were analyzed for CA-125 levels using a radioimmunoassay and the total protein was also measured. Normal individuals had low serum levels of sIL-2R alpha (367.5 +/- 44.6 U/mL), with similar levels of sIL-2R alpha in the normal peritoneal fluid (438.6 +/- 48.8 U/mL). In contrast, the serum and ascitic fluid levels in ovarian cancer patients were significantly higher (746.7 +/- 82.9 U/mL, P = .0006; 2,656.7 +/- 373.7 U/mL, P = .00002, respectively). The results for sIL-2R alpha were also significant when the levels were expressed per milligram of total protein. More importantly, in almost every ovarian cancer patient the ascitic sIL-2R alpha level far exceeded the serum level, a pattern also observed for CA-125. There was no correlation between the serum and ascitic sIL-2R alpha levels, or between the serum and ascitic CA-125 levels. Although the serum levels of sIL-2R alpha and CA-125 were elevated in the same patient, overall there was no correlation between the serum sIL-2R alpha and serum CA-125 levels, either when the levels were expressed in absolute units or per milligram of total protein. Similarly, there was no correlation between sIL-2R alpha and CA-125 levels in individual ascitic samples. While CA-125 levels may reflect an independent index of tumor burden, these results suggest that selective accumulation of sIL-2R alpha in the ascites may be one of the factors associated with the known nonresponsiveness of the infiltrating lymphocytes against ovarian carcinoma cells.

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