scholarly journals Soluble IL-2R as a predictor of familial breast cancer

2019 ◽  
Author(s):  
Kenji Gonda ◽  
Shoichiro Horita ◽  
Yuko Maejima ◽  
Seiichi Takenoshita ◽  
Kenju Shimomura
Keyword(s):  
Breast Cancer ◽  
Familial Breast Cancer ◽  
Mononuclear Cells ◽  
Breast Cancer Patients ◽  
Peripheral Blood Mononuclear ◽  
Tissue Samples ◽  
Aggressive Cancer ◽  
Increased Risk ◽  
Immunosuppressive Cells ◽  
Cancer Tissues

Abstract Background: The incidence of breast cancer has been increasing annually, and breast cancer-related diseases, such as breast cancer in the young, ovarian cancer, prostate cancer, and pancreatic cancer, have clearly and steadily increased in number and have become common among the family members of patients with breast cancer. Accordingly, an increase in the incidence of familial breast cancer (FBC) is anticipated in the future. Interleukin (IL)-2 is one of the cytokines that activate CTLs, which are important for cancer immunity. To search for the markers of increased risk for FBC, we examined the sIL-2R levels and immunologic factors in patients with breast cancer and nonfamilial breast cancer (NFBC). Methods: Of the 106 untreated breast cancer patients who gave consent to participate in this study, 24 had FBC and 82 had NFBC. There were 11 healthy individuals included in this study. Serum and peripheral blood mononuclear cells were collected from all patients for the measurement of the levels of sIL-2R, IL-10, VEGF, IL-17, Tregs, and MDSC. Prognosis was assessed and compared, according to the sIL-2R levels (low vs. high). Tissue samples from postoperative patients with high sIL2 were stained with PD-LI and CD8. Results: The sIL-2R level was significantly higher and had significantly better correlations with IL-10, VEGF, IL-17, Tregs, and MDSC levels in FBC than in NFBC. In cases with high sIL-2R level, the Tregs and MDSC levels were significantly higher and the OS and DFS rates were significantly worse in FBC than in NFBC. Among the FBC cases with high sIL-2R level, triple-negative breast cancer tissues stained well for PD-LI and CD8. Conclusions: Compared with NFBC, FBC was associated with higher sIL-2R levels, Th2 significance, and less aggressive cancer immunosuppressive cells. We have identified sIL-2R as a biomarker that can predict the prognosis of FBC. The ability to prospectively identify patients who are less likely to have NFBC is a vital step in improving the overall survival of this population.

scholarly journals Soluble IL-2R as a predictor of familial breast cancer

2020 ◽  
Author(s):  
Kenji Gonda ◽  
Shoichiro Horita ◽  
Yuko Maejima ◽  
Seiichi Takenoshita ◽  
Kenju Shimomura
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Familial Breast Cancer ◽  
Mononuclear Cells ◽  
Disease Free Survival ◽  
Suppressor Cells ◽  
Breast Cancer Patients ◽  
Peripheral Blood Mononuclear ◽  
Tissue Samples ◽  
Increased Risk

Abstract Background: The incidence of breast cancer has been increasing annually, and breast cancer-related diseases, such as breast cancer in the young, ovarian cancer, prostate cancer, and pancreatic cancer, have clearly and steadily increased in number and have become common among the family members of patients with breast cancer. Accordingly, an increase in the incidence of familial breast cancer (FBC) is anticipated in the future. Interleukin (IL)-2 is one of the cytokines that activate cytotoxic T lymphocytes (CTLs), which are important for cancer immunity. To identify the markers of increased risk for FBC, soluble IL-2 receptor (sIL-2R) levels and immunologic factors were investigated in patients with FBC and non-familial breast cancer (NFBC).Methods: Of the 106 untreated breast cancer patients who gave consent to participate in this study, 24 had FBC and 82 had NFBC. There were 11 healthy individuals included in this study. Serum and peripheral blood mononuclear cells were collected from all patients for measurement of sIL-2R, IL-10, Vascular endothelial growth factor (VEGF), IL-17, regulatory T cells (Tregs), Myeloid derived suppressor cells (MDSCs), neutrophil to lymphocyte ratio (NLR), white blood cell (WBC) and C-reactive protein (CRP) levels. Prognosis was assessed and compared according to sIL-2R levels (low vs. high). Tissue samples from postoperative patients with high sIL-2R levels were stained with programmed cell death ligand 1 (PD-L1) and Cluster of Differentiation (CD) 8.Results: sIL-2R level was significantly higher and had significantly stronger correlation with IL-10, VEGF, IL-17, Tregs, MDSCs levels, NLR, WBC count and CRP in FBC, than in NFBC. In cases with high sIL-2R levels, Tregs and MDSCs levels were significantly higher and the overall survival (OS) and disease free survival (DFS) rates were significantly worse in FBC than in NFBC. Among the FBC cases with high sIL-2R levels, triple negative breast cancer tissues stained well for PD-L1and CD8.Conclusions: Compared with NFBC, FBC was associated with higher sIL-2R level, Th2 predominance, and less aggressive cancer immunosuppressive cells. In the present study, sIL-2R was identified as a biomarker that can predict the prognosis of FBC. The ability to prospectively identify patients who are less likely to have NFBC is a vital step in improving the overall survival of this population.

scholarly journals Epithelial/Mesenchymal Characteristics and PD-L1 Co-Expression in CTCs of Metastatic Breast Cancer Patients Treated with Eribulin: Correlation with Clinical Outcome

Cancers ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3735
Author(s):  
Hara Polioudaki ◽  
Anastasia Mala ◽  
Eleni Gkimprixi ◽  
Maria A. Papadaki ◽  
Amanda Chantziou ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Mononuclear Cells ◽  
Cox Regression ◽  
Metastatic Breast ◽  
Breast Cancer Patients ◽  
Peripheral Blood Mononuclear ◽  
Cox Regression Analysis ◽  
Risk Of Death ◽  
Increased Risk

We aimed to evaluate the co-expression of PD-L1 and epithelial-mesenchymal markers in CTCs from metastatic breast cancer (MBC) patients and to determine if there is any relationship with patients’ outcome after eribulin treatment. Using cytospin preparations of peripheral blood mononuclear cells (PBMCs) from MBC patients treated with eribulin and a combination of immunocytochemistry and immunofluorescence, we quantified PD-L1, keratins and vimentin in single and cluster CTCs on days 1 and 8 of the first-treatment cycle. CTCs (n = 173) were found in 31 out of 38 patients. At baseline, the presence of cluster CTCs (p = 0.048), cluster mesenchymal CTCs (mCTCs) (p = 0.0003) or cluster PD-L1+mCTCs (p = 0.006) was associated with shorter overall survival (OS). In multivariate cox regression analysis, the detection of cluster mCTCs was the only parameter associated with increased risk of death (p = 0.024). On day 8 post-eribulin administration, PD-L1+mCTCs and especially single PD-L1+mCTCs decreased in 75% and 89% of patients, respectively. The detection of single PD-L1+mCTCs after eribulin treatment was correlated with shorter PFS (p = 0.047) and OS (p = 0.020). In conclusion, our study identified for the first time that cluster and single PD-L1+mCTCs subpopulations are of clinical significance in patients with MBC and highlighted the importance of CTC phenotyping during treatment with eribulin.

Immunoglobulin G fragment C receptor polymorphisms and response to trastuzumab-based treatment in patients with HER-2/neu-positive metastatic breast cancer

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 13090-13090 ◽  
Author(s):  
A. Musolino ◽  
N. Naldi ◽  
B. Bortesi ◽  
M. Capelletti ◽  
D. Pezzuolo ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Immunoglobulin G ◽  
Mononuclear Cells ◽  
Metastatic Breast ◽  
Cancer Cell Line ◽  
Breast Cancer Patients ◽  
Peripheral Blood Mononuclear ◽  
Immune Effector ◽  
Her 2

13090 Background: A potential mechanism of action of the humanized anti-HER-2/neu monoclonal antibody Trastuzumab involves antibody-dependent cellular cytotoxicity (ADCC) with the activation of immune effector cells via their immunoglobulin G fragment C receptors (FcγRs). Trastuzumab has been shown to engage both activation (FcγRIIIa; FcγRIIa) and inhibitory (FcγRIIb) antibody receptors on myeloid cells and several FcγR polymorphisms have been identified that may affect the antibody-dependent cytotoxicity of natural killer cells and macrophages. Methods: Forty consecutive HER-2/neu-positive (FISH+) metastatic breast cancer patients receiving a trastuzumab-based treatment (combined with paclitaxel for the majority) were examined for the FcγRIIIa 158 valine (V)/phenylalanine (F), FcγRIIa 131 histidine (H)/arginine (R), and FcγRIIb 232 isoleucine (I)/threonine (T) polymorphisms. A PCR-RFLP based assay using genomic DNA was performed for FcγRIIIa and FcγRIIa genotyping, while PCR-SSCP methods using complementary DNA were utilized for FcγRIIb. Patients’ peripheral blood mononuclear cells were drawn before treatment initiation and their trastuzumab-mediated killing function was measured by 51Cr release using a HER-2/neu-expressing human breast cancer cell line as a target. The results were then correlated with clinical outcome of these patients. Results: Median age was 60 years (range 26–83 years). Thirty-six (90%) patients received a trastuzumab-based treatment as first-line therapy. The overall clinical benefit rate (CR+PR+SD) was 65% (95% Confidence Interval: 62–71%), including 8 (20%) complete and 11 (27.5%) partial responses. Median survival was 22.3 mo with a median PFS of 7 mo. Trastuzumab-based treatment was well tolerated and no changes in cardiac function were observed. Conclusions: This study evaluates for the first time the potential role of FcγR polymorphisms in predicting response to trastuzumab-based treatment. Results according to this study purpose will be presented at the meeting. No significant financial relationships to disclose.

Correlation between NK function and response to trastuzumab in metastatic breast cancer

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 3036-3036
Author(s):  
A. Beano ◽  
E. Signorino ◽  
M. A. Polimeni ◽  
M. Mistrangelo ◽  
M. Ardine ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Nk Cells ◽  
Disease Progression ◽  
Mononuclear Cells ◽  
Metastatic Breast ◽  
Nk Activity ◽  
Breast Cancer Patients ◽  
Her2 Positive ◽  
Peripheral Blood Mononuclear ◽  
Effector Cells

3036 Background: Trastuzumab is a monoclonal antibody selectively directed against Her2 approved for the treatment of Her2 overexpressing breast cancer patients. Its proposed mechanisms of action include also a role in mediating antibody-dependent cellular cytotoxicity (ADCC), through the triggering of the FcγRIII on natural killer (NK) cells. This study addressed the correlation between overall NK function and clinical trastuzumab activity. Methods: Between March and September 2006 22 metastatic patients in treatment with trastuzumab alone (8 mg/kg load and then 6 mg/kg every 3 weeks until disease progression) as maintaining therapy after chemotherapy were analyzed for clinical and immunological responses. According to RECIST criteria, 14 patients obtained a response to trastuzumab, while 8 patients had a disease progression. Patient’s peripheral blood mononuclear cells were tested for cytotoxic activity against standard NK target (the MHC class I-negative K562 cell line) and trastuzumab-coated MCF7 (Her2-negative) and SKBR3 (Her2-positive) human cell lines in a 4-h 51Cr-release cytotoxicity assay in the presence of grading concentrations of effector cells. Results: NK activity was significantly (p<0.05) higher in responder compared to non responder patients at all the four effector:target (50:1 to 6:1) ratios tested. NK activity of non responder patients was significantly lower than that of 25 sex and age matched controls (p<0.02) and this was not merely due to chemotherapy- or tumor-associated immunosuppression, since the values of responder patients did not significantly differ from those of controls. ADCC activity against Her2-positive SKBR3 cells was also significantly higher in responder compared to non responder patients (p<0.05) and markedly so when compared to controls (p<0.001). Conclusions: The fact that, as shown here, normal levels of FcγR- independent and higher than normal levels of FcγR-dependent cytotoxicity are required for trastuzumab response, lends support to a paramount role of NK cells in the mechanism of action of this drug. No significant financial relationships to disclose.

scholarly journals Clinical Relevance of Immune Checkpoints on Circulating Tumor Cells in Breast Cancer

Cancers ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 376 ◽  
Author(s):  
Maria A. Papadaki ◽  
Anastasios V. Koutsopoulos ◽  
Panormitis G. Tsoulfas ◽  
Eleni Lagoudaki ◽  
Despoina Aggouraki ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Peripheral Blood ◽  
Tumor Tissue ◽  
Mononuclear Cells ◽  
Immune Checkpoints ◽  
Peripheral Blood Mononuclear ◽  
Increased Risk

The role of CD47 and PD-L1 expression on circulating tumor cells (CTCs) remains unclear, and it is currently unknown whether their distribution varies between the blood and tumor tissue in breast cancer (BC). In this study, CD47 and PD-L1 expression was investigated a) on peripheral blood mononuclear cell (PBMC) cytospins from early (n = 100) and metastatic (n = 98) BC patients, by triple immunofluorescence for CD47/PD-L1/Cytokeratins, and b) on matched primary and/or metastatic tumor tissue from CTC-positive patients using immunohistochemistry. CD47+and/orPD-L1+ CTCs were detected in 11%, 16.9%, and 29.6% of early, recurrent, and de novo metastatic patients (p = 0.016). In metastatic disease, CD47highand/orPD-L1high CTCs were associated with disease progression (p = 0.005) and shorter progression-free survival (PFS) (p = 0.010), and independently predicted for an increased risk of relapse (HR: 2.719; p = 0.008) and death (HR: 2.398; p = 0.034). PD-L1 expression rates differed between CTCs and tissue tumor cells and between peripheral blood mononuclear cells (PBMCs) and tumor-infiltrating lymphocytes (TILs) (positive concordance of 3.8% and 4%, respectively). CD47 expression also differed between CTCs and tumor cells (positive concordance of 11.5%). In conclusion, CTCs expressing CD47 and PD-L1 have independent poor prognostic implications in metastatic BC, indicating a potential role of innate and adaptive immune evasion mechanisms in their metastatic potential. The clinical value of the parallel assessment of the peripheral and local immune response merits further evaluation in BC.

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