scholarly journals Phenotypical and functional properties of generated dendritic cells in lung cancer patients

2016 ◽  
Vol 4 (2) ◽  
pp. 162-166 ◽  
Author(s):  
N. Khranovska ◽  
O. Skachkova ◽  
V. Sovenko ◽  
P. Sydor ◽  
M. Inomistova ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Dendritic Cells ◽  
Cancer Patients ◽  
Combined Treatment ◽  
Lower Amount ◽  
Functional Characteristics ◽  
Lung Cancer Patients ◽  
Healthy Donors ◽  
Dc Vaccines ◽  
Antitumor Vaccine

This study aimed to investigate phenotypical and functional characteristics of dendritic cells (DCs) generated from monocytes of peripheral blood of healthy donors and cancer patients.Material and methods. DCs were used as natural adjuvants with antitumor vaccine as a part of combined treatment scheme for lung cancer patients. Phenotypical and functional characteristics of DCs were study using flow cytometry and real-time PCR.Results. We have found that in lung cancer patients generated DCs had moderate level of maturity and demonstrated more pronounced tolerogenic features in contrast to DCs of healthy donors (patients DCs had higher mRNA expression levels of suppressive molecules TGF-β and IDO, and secreted lower amount of bioactive IL-12 protein). Expression of CCR7 gene was particularly on the normal level in DCs of cancer patients which indicates on saving of migratory properties of these cells. Expression level of DC maturity marker CD83 increased after each subsequent vaccine administration, while the levels of TGF-β, IL-10 mRNAs to the end of vaccine therapy course decreased to the level observed in healthy donors DCs.Conclusion. Thus, the study of biological characteristics of DCs will help to improve and develop the most effective protocols for rational use of DC vaccines. These data indicate the need for further optimization of technologies of DC generation in patients with lung cancer with emphasis on the stimulation of Th1-polarizing properties by increasing cytokine-secreting potential.

scholarly journals CD11c- and CD123-positive dendritic cells in development of antitumour immunity in non-small cell lung cancer patients

2019 ◽  
Vol 70 (2) ◽  
pp. 109-114 ◽  
Author(s):  
Plamen Minkov ◽  
Maya Gulubova ◽  
Koni Ivanova ◽  
Evelin Obretenov ◽  
Julian Ananiev
Keyword(s):  
Lung Cancer ◽  
Dendritic Cells ◽  
Small Cell Lung Cancer ◽  
Cancer Patients ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Small Cell Lung ◽  
Lung Cancer Patients

scholarly journals High PD-L1/CD274 Expression of Monocytes and Blood Dendritic Cells Is a Risk Factor in Lung Cancer Patients Undergoing Treatment with PD1 Inhibitor Therapy

Cancers ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 2966
Author(s):  
Dagmar Riemann ◽  
Wolfgang Schütte ◽  
Steffi Turzer ◽  
Barbara Seliger ◽  
Miriam Möller
Keyword(s):  
Lung Cancer ◽  
Dendritic Cells ◽  
Risk Factor ◽  
Cancer Patients ◽  
Peripheral Blood ◽  
Therapy Response ◽  
Inhibitor Therapy ◽  
Strong Positive Correlation ◽  
Blood Monocytes ◽  
Lung Cancer Patients

The aim of this study was to investigate the expression of the coinhibitory molecule PD-L1/CD274 in monocytes and dendritic cells (DC) in the blood of lung cancer patients undergoing PD1 inhibitor therapy and to correlate data with patient’s outcome. PD-L1/CD274 expression of monocytes, CD1c+ myeloid DC (mDC) and CD303+ plasmacytoid DC (pDC) was determined by flow cytometry in peripheral blood at immunotherapy onset. The predictive value of the PD-L1/CD274-expression data was determined by patients’ survival analysis. Patients with a high PD-L1/CD274 expression of monocytes and blood DC subpopulations rarely responded to PD1 inhibitor therapy. Low PD-L1/CD274 expression of monocytes and DC correlated with prolonged progression-free survival (PFS) as well as overall survival (OS). The highest PD-L1/CD274 expression was found in CD14+HLA-DR++CD16+ intermediate monocytes. Whereas the PD-L1/CD274 expression of monocytes and DC showed a strong positive correlation, only the PD-L1/CD274 expression of DC inversely correlated with DC amounts and lymphocyte counts in peripheral blood. Our results implicate that a high PD-L1/CD274 expression of blood monocytes and DC subtypes is a risk factor for therapy response and for the survival of lung cancer patients undergoing PD1 inhibitor therapy.

scholarly journals Lipid Accumulation in Peripheral Blood Dendritic Cells and Anticancer Immunity in Patients with Lung Cancer

2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Ryo Arai ◽  
Sayo Soda ◽  
Tomoko Okutomi ◽  
Hiroko Morita ◽  
Fumito Ohmi ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Dendritic Cells ◽  
Cancer Patients ◽  
Peripheral Blood ◽  
Lipid Accumulation ◽  
Stage Iii ◽  
Advanced Lung Cancer ◽  
Lung Cancer Patients ◽  
Treatment Naïve ◽  
Anticancer Immunity

We studied the subsets of peripheral blood dendritic cells (DCs) and lipid accumulation in DCs to investigate the involvement of DCs in the decreased anticancer immunity of advanced lung cancer patients. We analyzed the population of DC subsets in peripheral blood using flow cytometry. We then determined lipid accumulation in the DCs using BODIPY 650/665, a fluorophore with an affinity for lipids. Compared with healthy controls, the number of DCs in the peripheral blood of treatment-naive cancer patients was significantly reduced. In patients with stage III + IV disease, the numbers of myeloid DCs (mDCs) and plasmacytoid DCs were also significantly reduced. Lipid accumulation in DCs evaluated based on the fluorescence intensity of BODIPY 650/665 was significantly higher in stage III + IV lung cancer patients than in the controls. In the subset analysis, the fluorescence was highest for mDCs. The intracellularly accumulated lipids were identified as triglycerides. A decreased mixed leukocyte reaction was observed in the mDCs from lung cancer patients compared with those from controls. Taken together, the results show that lung cancer patients have a notably decreased number of peripheral blood DCs and their function as antigen-presenting cells is decreased due to their high intracellular lipid accumulation. Thereby, anticancer immunity is suppressed.

Efficient in vitro expression of the human reverse transcriptase (hTERT) but impaired maturation in dendritic cells of lung cancer patients

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 13518-13518
Author(s):  
B. Gahn ◽  
A. Brill ◽  
I. Bolz ◽  
W. Klapper ◽  
N. Schub ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Dendritic Cells ◽  
Cancer Patients ◽  
Fluorescent Protein ◽  
Transfection Efficiency ◽  
Telomerase Activity ◽  
Htert Mrna ◽  
Lung Cancer Patients ◽  
Wide Range ◽  
Mrna Transfection

13518 An innovative treatment strategy for patients with lung cancer is the targeting of tumor associated antigens with cellular effector cells. The telomerase catalytic subunit (hTERT) is an attractive target for cytotoxic T cells that is highly expressed in both NSCLC and SCLC cells. The aim of the study was the expression of hTERT in dendritic cells (DC) that are the most powerful antigen presenting cells for the induction of cellular immune responses. We used electrotransfection of DC with hTERT mRNA that enables an HLA independent whole antigen approach potentially targeting a wide range of hTERT epitopes. Immature DC were prepared from peripheral blood monocytes in serum-free growth medium, GM-CSF and IL-4. Subsequently the DC were electroporated with mRNA and matured in a cytokine cocktail consisting of IL-1 beta, IL-6, TNF-alpha and PGE2. Verification of hTERT mRNA transfection efficiency was performed by analyzing the induction of telomerase activity with the TRAP assay, the efficiency of GFP electrotransfection was determined by FACS. To optimize mRNA electrotransfection conditions the DCs of 3 healthy individuals were transfected with green fluorescent protein (GFP) mRNA. The percentage of electrotransfected DC was in between 18–89% (mean 46%). Subsequently we electrotransfected DCs in 3 lung cancer patients (1 SCLC, 2 NSCLC). In 1 patient GFP mRNA transfection resulted in 62% GFP positive DC. In the 2 other patients the telomerase activity in the DC 24 hrs after hTERT electrotransfection was equivalent to HL60 cells that biologically express high levels of hTERT. Importantly the DC of one patient did not mature after electrotransfection and incubation in the maturation cocktail. The same was true in another patient, in whom an electrotransfection was not done. In both patients the DC were expressing high levels of HLA-DR and no lineage markers, but CD83 as an indicator of maturation was found in only 1% and 9% respectively. Also the costimulatory molecules CD80 and CD86 were expressed at low levels only. These data show that strong hTERT expression can be achieved in DCs of lung cancer patients using mRNA electrotransfection but demontrate the need for other more potent maturation stimuli. No significant financial relationships to disclose.

Prospective phase II study of post-surgical adjuvant chemo-immunotherapy using autologous dendritic cells and activated killer cells from tissue culture of tumor draining lymph nodes in primary lung cancer patients

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 3048-3048
Author(s):  
H. Kimura ◽  
T. Iizasa ◽  
A. Ishikawa
Keyword(s):  
Lung Cancer ◽  
Tissue Culture ◽  
Dendritic Cells ◽  
Lymph Nodes ◽  
Cancer Patients ◽  
Phase Ii Study ◽  
Primary Lung Cancer ◽  
Killer Cells ◽  
Lung Cancer Patients ◽  
Draining Lymph Nodes

3048 Background: We conducted a phase II study to evaluate the efficacy and toxicity of adjuvant chemo-immunotherapy using dendritic cells and activated killer cells from tissue culture of tumor-draining lymph nodes (TDLN) in primary lung cancer patients. Methods: Pathological N2 lung cancer patients were selected for the post-surgical adjuvant chemo-immunotherapy. Activated killer cells and dendritic cells obtained from tissue cultures of TDLN or TDLN co-cultured with peripheral blood lymphocytes (TDLN-Pb) were used for the adoptive transfer of immunotherapy. Patients received 4 courses of post-surgical chemotherapy or chemotherapy along with immunotherapy (immunotherapy group) every 2 months for 2 years. Results: There were 57 N2 patients eligible for the study, 28 for immunotherapy and 29 for chemotherapy. For the 28 immunotherapy cases, a total of 313 courses of immunotherapy were administered. The main toxicities were fever (78.0%), chill (83.4%). The 5-year survival rates in the immunotherapy and chemotherapy groups were 56.5% and 12.5% respectively. Among the variables analyzed, immunotherapy was the most significant independent prognostic factor (p=0.0042.) Conclusions: Adoptive transfer of activated killer cells and dendritic cells from the tumor draining lymph nodes of primary lung cancer patients is safe and feasible, and a large-scale multi-institutional study is necessary for the evaluation of the efficacy of this treatment. No significant financial relationships to disclose.

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