Microenvironment generated during EGFR targeted killing of pancreatic tumor cells by ATC inhibits myeloid-derived suppressor cells through COX2 and PGE2 dependent pathway

Autor: Lawrence G. Lum, Fazlul H. Sarkar, Sri Vidya Kondadasula, Hiroshi Yano, Dana Schalk, Archana Thakur, Elyse N. Tomaszewski
Rok vydání: 2013
Předmět:
T-Lymphocytes
Activated T-cells
Bispecific antibody
T cell
Cellular differentiation
medicine.medical_treatment
Biology
Dinoprostone
General Biochemistry
Genetics and Molecular Biology
CCL5
03 medical and health sciences
0302 clinical medicine
Tumor Microenvironment
medicine
Humans
CXCL10
Cell Proliferation
Medicine(all)
Tumor microenvironment
Epidermal growth factor receptor
Biochemistry
Genetics and Molecular Biology(all)
Research
3D culture model
Cell Differentiation
Pancreatic cancer
General Medicine
Immunotherapy
Flow Cytometry
Coculture Techniques
3. Good health
ErbB Receptors
Killer Cells
Natural
Pancreatic Neoplasms
medicine.anatomical_structure
Cyclooxygenase 2
Tumor progression
Myeloid derived suppressor cells
030220 oncology & carcinogenesis
Immunology
Cancer research
Myeloid-derived Suppressor Cell
Cytokines
030215 immunology
Zdroj: Journal of Translational Medicine
ISSN: 1479-5876
DOI: 10.1186/1479-5876-11-35
Popis: Background Myeloid-derived suppressor cells (MDSCs) are one of the major components of the immune-suppressive network, play key roles in tumor progression and limit therapeutic responses. Recently, we reported that tumor spheres formed by breast cancer cell lines were visibly smaller in a Th1 enriched microenvironment with significantly reduced differentiation of MDSC populations in 3D culture. In this study, we investigated the mechanism(s) of bispecific antibody armed ATC mediated inhibition of MDSC in the presence or absence of Th1 microenvironment. Methods We used 3D co-culture model of peripheral blood mononuclear cells (PBMC) with pancreatic cancer cells MiaPaCa-2 [MiaE] and gemcitabine resistant MiaPaCa-GR [MiaM] cells to generate MDSC in the presence or absence of Th1 cytokines and EGFRBi armed ATC (aATC). Results We show significantly decreased differentiation of MDSC (MiaE, p
Databáze: OpenAIRE
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