دورية أكاديمية

Biological and molecular studies on specific immune cells treated with checkpoint inhibitors for the thera-personal approach of breast cancer patients ( ex-vivo study).

التفاصيل البيبلوغرافية
العنوان: Biological and molecular studies on specific immune cells treated with checkpoint inhibitors for the thera-personal approach of breast cancer patients ( ex-vivo study).
المؤلفون: El-Houseini ME; Medical Biochemistry and Molecular Biology, Cancer Biology Department, National Cancer Institute, Cairo University, Cairo, 11976, Egypt., Arafat MS; Biotechnology Department, Faculty of Science, Cairo University, Giza, 12613, Egypt., El-Husseiny AM; Zoology department, Faculty of Science, Cairo University, Giza, 12613, Egypt., Kasem IM; Biotechnology Department, Faculty of Science, Cairo University, Giza, 12613, Egypt., Kamel MM; Clinical Pathology Department, National Cancer Institute, Cairo University, Cairo, 11976, Egypt., El-Habashy AH; Department of Pathology, National Cancer Institute, Cairo University, Cairo, 11976, Egypt., Khafagy MM; Surgical Oncology Department, National Cancer Institute, Cairo University, Cairo, 11976, Egypt., Radwan EM; Clinical Pathology Department, National Cancer Institute, Cairo University, Cairo, 11976, Egypt., Helal MH; Radio-Diagnosis Department, National Cancer Institute, Cairo University, Cairo, 11976, Egypt., Abdellateif MS; Medical Biochemistry and Molecular Biology, Cancer Biology Department, National Cancer Institute, Cairo University, Cairo, 11976, Egypt.
المصدر: Oncology research [Oncol Res] 2022 Oct 10; Vol. 29 (5), pp. 319-330. Date of Electronic Publication: 2022 Oct 10 (Print Publication: 2021).
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Tech Science Press Country of Publication: United States NLM ID: 9208097 Publication Model: eCollection Cited Medium: Internet ISSN: 1555-3906 (Electronic) Linking ISSN: 09650407 NLM ISO Abbreviation: Oncol Res Subsets: MEDLINE
أسماء مطبوعة: Publication: 2021- : Henderson, NV : Tech Science Press
Original Publication: New York : Pergamon Press, c1992-
مواضيع طبية MeSH: Vascular Endothelial Growth Factor A* , Neoplasms*, Humans ; Animals ; Female ; Immunotherapy ; Coculture Techniques ; Down-Regulation ; Forkhead Transcription Factors
مستخلص: 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.
Competing Interests: The authors declare that they have no conflicts of interest to report regarding the present study.
(© 2022 El-Houseini et al.)
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فهرسة مساهمة: Keywords: CTLA4; Immunotherapy; PD1; TIDCs; TILs; breast cancer
المشرفين على المادة: 0 (Vascular Endothelial Growth Factor A)
0 (Forkhead Transcription Factors)
تواريخ الأحداث: Date Created: 20230612 Date Completed: 20230613 Latest Revision: 20231102
رمز التحديث: 20231102
مُعرف محوري في PubMed: PMC10207991
DOI: 10.32604/or.2022.025249
PMID: 37305162
قاعدة البيانات: MEDLINE