Open Access

ARTICLE

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

by MOTAWA E. EL-HOUSEINI¹, MOSTAFA S. ARAFAT², AHMED M. EL-HUSSEINY³, ISLAM M. KASEM², MAHMOUD M. KAMEL⁴, AHMED H. EL-HABASHY⁵, MEDHAT M. KHAFAGY⁶, ENAS M. RADWAN⁴, MAHA H. HELAL⁷, MONA S. ABDELLATEIF^1,*

1 Medical Biochemistry and Molecular Biology, Cancer Biology Department, National Cancer Institute, Cairo University, Cairo, 11976, Egypt
2 Biotechnology Department, Faculty of Science, Cairo University, Giza, 12613, Egypt
3 Zoology department, Faculty of Science, Cairo University, Giza, 12613, Egypt
4 Clinical Pathology Department, National Cancer Institute, Cairo University, Cairo, 11976, Egypt
5 Department of Pathology, National Cancer Institute, Cairo University, Cairo, 11976, Egypt
6 Surgical Oncology Department, National Cancer Institute, Cairo University, Cairo, 11976, Egypt
7 Radio-Diagnosis Department, National Cancer Institute, Cairo University, Cairo, 11976, Egypt

* Corresponding Author: MONA S. ABDELLATEIF. Email:

Oncology Research 2021, 29(5), 319-329. https://doi.org/10.32604/or.2022.025249

Received 09 July 2022; Accepted 15 September 2022; Issue published 10 October 2022

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.

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