@Article{or.2022.025249, AUTHOR = {MOTAWA E. EL-HOUSEINI, MOSTAFA S. ARAFAT, AHMED M. EL-HUSSEINY, ISLAM M. KASEM, MAHMOUD M. KAMEL, AHMED H. EL-HABASHY, MEDHAT M. KHAFAGY, ENAS M. RADWAN, MAHA H. HELAL, MONA S. ABDELLATEIF}, TITLE = {Biological and molecular studies on specific immune cells treated with checkpoint inhibitors for the thera-personal approach of breast cancer patients (ex-vivo study)}, JOURNAL = {Oncology Research}, VOLUME = {29}, YEAR = {2021}, NUMBER = {5}, PAGES = {319--329}, URL = {http://www.techscience.com/or/v29n5/50096}, ISSN = {1555-3906}, ABSTRACT = {Immunotherapy becomes a promising line of treatment for breast cancer (BC) however, its success rate is still limited. Methods: The study was designed to optimize the condition for producing an effective dendritic cell (DCs) based immunotherapy by using DCs and T lymphocytes together with tumor-infiltrating lymphocytes (TILs) and tumor-infiltrating DCs (TIDCs), treated with anti-PD1 and anti-CTLA4 monoclonal antibodies. This mixture of immune cells was co-cultured with autologous breast cancer cells (BCCs) isolated from 26 BC females. Results: There was a significant upregulation of CD86 and CD83 on DCs (P = 0.001 and 0.017, respectively), similarly upregulation of CD8, CD4 and CD103 on T cells (P = 0.031, 0.027, and 0.011, respectively). While there was a significant downregulation of FOXP3 and combined CD25.CD8 expression on regulatory T cells (P = 0.014 for both). Increased CD8/Foxp3 ratio (P < 0.001) was also observed. CD133, CD34 and CD44 were downregulated on BCCs (P = 0.01, 0.021, and 0.015, respectively). There was a significant increase in interferon-γ (IFN-γ, P < 0.001), lactate dehydrogenase (LDH, P = 0.02), and a significant decrease in vascular endothelial growth factor (VEGF, P < 0.001) protein levels. Gene expression of FOXP3 and Programmed cell death ligand 1 (PDL-1) were downregulated in BCCs (P < 0.001, for both), similarly cytotoxic T lymphocyte antigen-4 (CTLA4, P = 0.02), Programmed cell death 1 (PD-1, P < 0.001) and FOXP3 (P < 0.001) were significantly downregulated in T cells. Conclusion: Ex-vivo activation of immune cells (DCs, T cells, TIDCs, and TILs) with immune checkpoint inhibitors could produce a potent and effective BC immunotherapy. However, these data should be validated on an experimental animal model to be transferred to the clinical setting.}, DOI = {10.32604/or.2022.025249} }