Abstract 759: Sunitinib has opposite roles to regulate the myeloid-derived suppressor cells in tumors and peripheral blood

6070 Background: Patients with advanced stage squamous cell carcinoma of the head and neck (SCCHN) have less than 50% 5-year survival rate Human papillomavirus (HPV)-associated SCCHN in oropharyngeal sites have shown better prognosis. Little is known about the role of myeloid-derived suppressor cells (MDSCs) in immune suppression or tumor progression in the setting of SCCHN. Our objective is to evaluate the clinical significance of MDSCs in subjects with SCCHN, HPV-positivity, and advanced cancer staging. Methods: Thirty-three subjects with SCCHN and 10 healthy donors were enrolled in this prospective cohort study. Fresh blood was collected at the time of surgical resection of SCCHN in a tertiary academic center between August 2011 and January 2013. Peripheral blood mononuclear cells (PBMCs) were obtained using Ficoll Hypaque. MDSCs were immunophenotyped as CD14-CD33+CD11b+by flow cytometry. HPV status was determined by in situ hybridization Frequencies of MDSCs in blood of different cohorts were evaluated. Results: Thirty-three subjects (ages 34-83 years, 25 males) with SCCHN were enrolled. Increased numbers of CD14-CD33+CD11b+ cells of total leukocytes were found in HPV-associated SCCHN (median 26.6%, n=11) compared to HPV-negative SCCHN (16.3%, n=19). Interestingly, 3 subjects who previously had HPV-positive SCCHN but with no evidence of disease had 6.24% (n=3) CD14-CD33+CD11b+cells of leukocytes which was higher than healthy donors (3.55%, n=10). Subjects with advanced cancer stages (III-IV) had higher levels of MDSCs (26%, n=19) compared to those with a lower grade (I-II, 15.5%, n=11) regardless of HPV status. Three subjects were lost to follow up. Of the remaining subjects, the overall median follow time was 3 months and subjects who were found to have recurrence, regional or local metastasis had higher frequencies of MDSCs in the blood (26.35%, n=4) compared to those with no evidence of disease (18.5%, n=26) at the time of surgery. Conclusions: This study suggests there is an accumulation of MDSCs in peripheral blood of patients with SCCHN, particularly in HPV-associated SCCHN. Further, increased levels of MDSCs in the peripheral blood are related to more advance cancer stage and poor clinical outcomes.

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Evolution of the myeloid-derived suppressor cells in advanced breast cancer and comparative analysis with a healthy population cohort.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.2543 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. 2543-2543

Author(s):

Natalia Palazón-Carrión ◽

Carlos Jiménez-Cortegana ◽

Esther Holgado ◽

Josefina Cruz Jurado ◽

Jose Luis Alonso Romero ◽

...

Keyword(s):

Breast Cancer ◽

Advanced Breast Cancer ◽

Peripheral Blood ◽

Suppressor Cells ◽

Complete Response ◽

Advanced Breast ◽

Healthy Population ◽

Myeloid Derived Suppressor Cells ◽

Tumor Subtypes ◽

Disease Stabilization

2543 Background: High levels of myeloid-derived suppressor cells (MDSCs) seem a negative prognostic factor in advanced breast cancer (ABC) patients (pts). Preclinical studies suggest an immunomodulatory effect of some classical anti-tumor agents through alteration of MDSCs homeostasis. We analyzed the association of MDSCs and clinical evolution of ABC pts, taking into account the systemic treatment (tx) modulation of MDSCs levels in pts from two studies (“A”: GEICAM/2015-04 PANGEA-BREAST, NCT03025880 “Efficacy and Safety of Pembrolizumab and Gemcitabine in HER2-negative ABC”, and “B”: PI-0502-2014 “Peripheral blood analyses of immune response induced by 1st line tx of ABC according to clinical guidelines”). Methods: MDSCs (CD33+ CD11b+) levels were determined by flow-cytometry in peripheral blood samples at three time points (basal, at cycles 3 and 6) from: 39 HER2-negative heavily pretreated pts from study “A”, 43 non-pretreated pts (all subtypes) from study “B” and 20 women from a healthy cohort (HC), with no cancer diagnosis. MDSCs levels from the different cohorts were compared and correlated with pts with Clinical Benefit (CB: partial/complete response + disease stabilization) vs pts with Progressive Disease (PD). Results: Tx response was assessed in 33 pts (85%) from study “A” and 39 pts (91%) from study “B”. CB was observed in 11 pts (28%) from study “A” and in 34 (79%) from study “B” while PD was observed in 22 pts (56%) from study “A” and in 5 (12%) from study “B”. Basal MDSCs levels were significantly higher in ABC pts (studies “A”+”B”) than in HC (15.95 vs 0.81 cells/µl, p = 0.009). At cycle 6, MDSCs were considerably lower in pts with CB vs DP (2.90 vs 13.75 cells/µl, p < 0.001). This decrease was more pronounced in study “B” than in study “A” pts (p < 0.001 vs p = 0.074, respectively), probably due to differences in number of events, tumor subtypes and tx between both studies. Conclusions: Our results suggest that ABC pts show alterations in MDSCs and that their decrease along tx may have a positive predictive value, highlighting the importance that immune-competent status may play in the evolution of ABC. MDSCs may represent a target for therapeutic purposes in ABC.

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Interferon alpha-induced reduction in the values of myeloid-derived suppressor cells in melanoma patients

Vojnosanitetski pregled ◽

10.2298/vsp1504342s ◽

2015 ◽

Vol 72 (4) ◽

pp. 342-349 ◽

Cited By ~ 1

Author(s):

Ivan Stanojevic ◽

Milomir Gacevic ◽

Milena Jovic ◽

Zeljko Mijuskovic ◽

Rados Zecevic ◽

...

Keyword(s):

Interferon Alpha ◽

Peripheral Blood ◽

Suppressor Cells ◽

Healthy Controls ◽

Myeloid Derived Suppressor Cells ◽

Interferon Alpha Therapy ◽

Significant Difference ◽

Alpha Effect ◽

Melanoma Patients ◽

Alpha Therapy

Background/Aim. Interaction between tumor cells and host?s immunoregulatory cells in creation of microenvironment that supports tumor progression is the focus of numerous investigations in recent years. Myeloid-derived suppressor cells (MDSCs) are heterogeneous population of immature dendritic cells, macrophages and granulocytes. In cancer patients, these cells accumulate in tumor microenvironment, tumor-draining lymph nodes, peripheral blood and the liver and their numbers correlate with the stage of the disease and the metastatic disease. The aim of the study was to investigate the effect of interferon alpha on MDSCs percentage in peripheral blood of melanoma patients. Methods. The interferon treated melanoma patients were given subcutaneously interferon alpha, in optimal dose, for a period of at least 6 months before the analysis. Blood samples were collected from the melanoma patients (n = 91) and the age/sex matched healthy controls (n = 8). The following anti-human monoclonal antibodies were used for immunostaining: anti-CD15-FITC, anti-CD33-PE, anti-CD45-ECD, anti-HLA-DR PE/Cy5, anti-CD14-FITC, anti-CD16-PE and anti-CD11b-PE. Results. Comparison of myeloid-derived suppressor cells values in the stage 2 melanoma patients with and without interferon alpha therapy did not show a significant difference. When we compared the MDSCs values in the patients within stage 3 melanoma, we found a significant difference in granulocytic subset values between the interferon alpha-treated and the untreated group. Comparison of values of all suppressor cells populations between the interferon alpha-treated patients and healthy controls showed a significant increase in suppressor cells percentage in the melanoma patients. The granulocytic and total MDSCs values were significantly lower in the interferon alpha treated melanoma patients with progression in comparison with untreated patients with stable disease. Conclusion. We confirmed that interferon alpha effect in stage 3 melanoma patients was reduction in MDSCs percentage. We also found an unexpected bounce back of these suppressor cells levels, many months after the discontinuation of interferon alpha therapy.

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