Dendritic cells transfected with allel-specific polyepitope DNA-constructs stimulate cytotoxic response mononuclear cells of breast cancer patients in vitro

Abstract Although peripheral blood stem cell collections (PBSC) are thought to have less tumor involvement than bone marrow (BM), the incidence of circulating tumor cells in patients with breast cancer has not been widely investigated. We prospectively investigated the incidence and viability of tumor cell involvement in PBSC and BM collections from breast cancer patients undergoing high-dose chemotherapy/hematopoietic stem cell transplantation. Paired samples of PBSC and BM from 48 patients were analyzed using an immunocytochemical technique that detects one epithelial-derived tumor cell per 5 x 10(5) mononuclear cells. Immunostained tumor cells were detected in 9.8% (13/133) PBSC specimens from 9/48 (18.7%) patients and in 62.3% (38/61) BM specimens from 32/48 (66.7%) patients, a significantly higher rate than in PBSC (P < .005). The geometric mean concentration of tumor cells in contaminated PBSC specimens was 0.8/10(5) mononuclear cells (range 0.33 to 2.0/10(5)) compared with 22.9/10(5) mononuclear cells in BM (range 1 to 3,000/10(5), P < .0001). In culture experiments, clonogenic tumor colonies grew in 21/26 immunocytochemically positive specimens. No tumor colony growth was detected in 30/32 immunocytochemically negative specimens. Immunocytochemical detection of tumor involvement in BM and PBSC correlated significantly with in vitro clonogenic growth (P < .0001). We conclude that PBSC contain fewer tumor cells than paired BM specimens from patients with advanced breast cancer and that these tumor cells appear to be capable of clonogenic growth in vitro.

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Induction of an antitumor response using dendritic cells transfected with DNA constructs encoding the HLA-A*02:01-restricted epitopes of tumor-associated antigens in culture of mononuclear cells of breast cancer patients

Immunologic Research ◽

10.1007/s12026-015-8735-0 ◽

2015 ◽

Vol 64 (1) ◽

pp. 171-180 ◽

Cited By ~ 3

Author(s):

Sergey Vital’evich Sennikov ◽

Julia Alexandrovna Shevchenko ◽

Vasilii Vasil’evich Kurilin ◽

Julia Nikolaevna Khantakova ◽

Julia Anatol’evna Lopatnikova ◽

...

Keyword(s):

Breast Cancer ◽

Dendritic Cells ◽

Cancer Patients ◽

Mononuclear Cells ◽

Breast Cancer Patients ◽

Antitumor Response ◽

Tumor Associated Antigens

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In vitro Colony Assay of Peripheral Blood Mononuclear Cells – A Comparison of Breast Cancer Patients and Normal Individuals

Oncology ◽

10.1159/000225657 ◽

1982 ◽

Vol 39 (5) ◽

pp. 304-307

Author(s):

Leo F. Skinnider ◽

Donna E. Malcolm

Keyword(s):

Breast Cancer ◽

Cancer Patients ◽

Peripheral Blood Mononuclear Cells ◽

Mononuclear Cells ◽

Breast Cancer Patients ◽

Peripheral Blood Mononuclear ◽

Colony Assay ◽

Normal Individuals ◽

Blood Mononuclear Cells

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Restoration of Tumor-Specific HLA Class I Restricted Cytotoxicity in Tumor Infiltrating Lymphocytes of Advanced Breast Cancer Patients by in vitro Stimulation with Tumor Antigen-Pulsed Autologous Dendritic Cells

Breast Cancer Research and Treatment ◽

10.1023/a:1024938215782 ◽

2003 ◽

Vol 80 (3) ◽

pp. 275-285 ◽

Cited By ~ 10

Author(s):

Rena Kass ◽

Stefania Bellone ◽

Michela Palmieri ◽

Stefania Canè ◽

Eliana Bignotti ◽

...

Keyword(s):

Breast Cancer ◽

Dendritic Cells ◽

Advanced Breast Cancer ◽

Cancer Patients ◽

Tumor Antigen ◽

Tumor Infiltrating Lymphocytes ◽

Hla Class I ◽

Breast Cancer Patients ◽

Infiltrating Lymphocytes

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Detection and viability of tumor cells in peripheral blood stem cell collections from breast cancer patients using immunocytochemical and clonogenic assay techniques [see comments]

Blood ◽

10.1182/blood.v82.9.2605.bloodjournal8292605 ◽

1993 ◽

Vol 82 (9) ◽

pp. 2605-2610 ◽

Cited By ~ 6

Author(s):

AA Ross ◽

BW Cooper ◽

HM Lazarus ◽

W Mackay ◽

TJ Moss ◽

...

Keyword(s):

Breast Cancer ◽

Stem Cell ◽

Tumor Cell ◽

Cancer Patients ◽

Tumor Cells ◽

Mononuclear Cells ◽

Peripheral Blood Stem Cell ◽

Breast Cancer Patients ◽

Tumor Involvement

Although peripheral blood stem cell collections (PBSC) are thought to have less tumor involvement than bone marrow (BM), the incidence of circulating tumor cells in patients with breast cancer has not been widely investigated. We prospectively investigated the incidence and viability of tumor cell involvement in PBSC and BM collections from breast cancer patients undergoing high-dose chemotherapy/hematopoietic stem cell transplantation. Paired samples of PBSC and BM from 48 patients were analyzed using an immunocytochemical technique that detects one epithelial-derived tumor cell per 5 x 10(5) mononuclear cells. Immunostained tumor cells were detected in 9.8% (13/133) PBSC specimens from 9/48 (18.7%) patients and in 62.3% (38/61) BM specimens from 32/48 (66.7%) patients, a significantly higher rate than in PBSC (P < .005). The geometric mean concentration of tumor cells in contaminated PBSC specimens was 0.8/10(5) mononuclear cells (range 0.33 to 2.0/10(5)) compared with 22.9/10(5) mononuclear cells in BM (range 1 to 3,000/10(5), P < .0001). In culture experiments, clonogenic tumor colonies grew in 21/26 immunocytochemically positive specimens. No tumor colony growth was detected in 30/32 immunocytochemically negative specimens. Immunocytochemical detection of tumor involvement in BM and PBSC correlated significantly with in vitro clonogenic growth (P < .0001). We conclude that PBSC contain fewer tumor cells than paired BM specimens from patients with advanced breast cancer and that these tumor cells appear to be capable of clonogenic growth in vitro.

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Autologous Dendritic Cells in Combination With Chemotherapy Restore Responsiveness of T Cells in Breast Cancer Patients: A Single-Arm Phase I/II Trial

Frontiers in Immunology ◽

10.3389/fimmu.2021.669965 ◽

2021 ◽

Vol 12 ◽

Author(s):

David A. Bernal-Estévez ◽

Mauren A. Ortíz Barbosa ◽

Paola Ortíz-Montero ◽

Claudia Cifuentes ◽

Ramiro Sánchez ◽

...

Keyword(s):

Breast Cancer ◽

Flow Cytometry ◽

T Cells ◽

Dendritic Cells ◽

Adverse Effects ◽

Phase I ◽

Cancer Patients ◽

Functional Performance ◽

Breast Cancer Patients

IntroductionAnimal studies and preclinical studies in cancer patients suggest that the induction of immunogenic cell death (ICD) by neoadjuvant chemotherapy with doxorubicin and cyclophosphamide (NAC-AC) recovers the functional performance of the immune system. This could favor immunotherapy schemes such as the administration of antigen-free autologous dendritic cells (DCs) in combination with NAC-AC to profit as cryptic vaccine immunogenicity of treated tumors.ObjectiveTo explore the safety and immunogenicity of autologous antigen-free DCs administered to breast cancer patients (BCPs) in combination with NAC-AC.Materials and MethodsA phase I/II cohort clinical trial was performed with 20 BCPs treated with NAC-AC [nine who received DCs and 11 who did not (control group)]. The occurrence of adverse effects and the functional performance of lymphocytes from BCPs before and after four cycles of NAC-AC receiving DCs or not were assessed using flow cytometry and compared with that from healthy donors (HDs). Flow cytometry analysis using manual and automated algorithms led us to examine functional performance and frequency of different lymphocyte compartments in response to a stimulus in vitro. This study was registered at clinicaltrials.gov (NCT03450044).ResultsNo grade II or higher adverse effects were observed associated with the transfer of DCs to patients during NAC-AC. Interestingly, in response to the in vitro stimulation, deficient phosphorylation of Zap70 and AKT proteins observed before chemotherapy in most patients’ CD4 T cells significantly recovered after NAC-AC only in patients who received DCs.ConclusionsThe transfer of autologous DCs in combination with NAC-AC in BCPs is a safe procedure. That, in BCPs, the administration of DCs in combination with NAC-AC favors the recovery of the functional capacity of T cells suggests that this combination may potentiate the adjuvant effect of ICD induced by NAC-AC on T cells and, hence, potentiate the immunogenicity of tumors as cryptic vaccines.

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Targeting PKM2 promotes chemosensitivity of breast cancer cells in vitro and in vivo

Cancer Biomarkers ◽

10.3233/cbm-210111 ◽

2021 ◽

pp. 1-10

Author(s):

Yu Wang ◽

Han Zhao ◽

Ping Zhao ◽

Xingang Wang

Keyword(s):

Breast Cancer ◽

Neoadjuvant Chemotherapy ◽

Cancer Cells ◽

Cancer Patients ◽

Poor Prognosis ◽

Breast Cancer Cells ◽

Breast Cancer Patients ◽

Cancer Tissues

BACKGROUND: Pyruvate kinase M2 (PKM2) was overexpressed in many cancers, and high PKM2 expression was related with poor prognosis and chemoresistance. OBJECTIVE: We investigated the expression of PKM2 in breast cancer and analyzed the relation of PKM2 expression with chemotherapy resistance to the neoadjuvant chemotherapy (NAC). We also investigated whether PKM2 could reverse chemoresistance in breast cancer cells in vitro and in vivo. METHODS: Immunohistochemistry (IHC) was performed in 130 surgical resected breast cancer tissues. 78 core needle biopsies were collected from breast cancer patients before neoadjuvant chemotherapy. The relation of PKM2 expression and multi-drug resistance to NAC was compared. The effect of PKM2 silencing or overexpression on Doxorubicin (DOX) sensitivity in the MCF-7 cells in vitro and in vivo was compared. RESULTS: PKM2 was intensively expressed in breast cancer tissues compared to adjacent normal tissues. In addition, high expression of PKM2 was associated with poor prognosis in breast cancer patients. The NAC patients with high PKM2 expression had short survival. PKM2 was an independent prognostic predictor for surgical resected breast cancer and NAC patients. High PKM2 expression was correlated with neoadjuvant treatment resistance. High PKM2 expression significantly distinguished chemoresistant patients from chemosensitive patients. In vitro and in vivo knockdown of PKM2 expression decreases the resistance to DOX in breast cancer cells in vitro and tumors in vivo. CONCLUSION: PKM2 expression was associated with chemoresistance of breast cancers, and could be used to predict the chemosensitivity. Furthermore, targeting PKM2 could reverse chemoresistance, which provides an effective treatment methods for patients with breast cancer.

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