Tumor-activated dendritic cells pulsed CD8+ T cells injection reduced tumor necrosis in metastatic breast cancer mouse model
- Department of Biomedical Science, Advanced Medical and Dental Institute, Universiti Sains Malaysia, Bertam, 13200 Kepala Batas, Malaysia
- Department of Toxicology, Advanced Medical and Dental Institute, Universiti Sains Malaysia, Bertam, 13200 Kepala Batas, Malaysia
- Animal Research Facility, Advanced Medical and Dental Institute, Universiti Sains Malaysia, Bertam, 13200 Kepala Batas, Malaysia
- Pathology Department, School of Medical Sciences, Universiti Sains Malaysia, Health Campus, 16150 Kubang Kerian, Kelantan, Malaysia
- Nichi-Asia Life Science Sdn. Bhd., No. 57, Block F, Jalan Teknologi 3/9, Bistari De Kota, Kota Damansara, PJU 5, 47810 Petaling Jaya, Selangor, Malaysia
Abstract
Background: Different types of immune cells, such as tumor-specific T cells, natural killer (NK) cells and dendritic cells (DCs), are being studied for use in treating metastatic cancer. However, disease progression varies based on the source, type, and mode of administration of immune cells. The aim of the current study is to determine the effect of intravenous administration of human peripheral blood-derived CD8+ T cells and tumor-activated monocyte-derived dendritic cells (moDCs) pulsed CD8+ T cells on a human metastatic breast cancer mouse model.
Methods: A total of nine NOD.SCID gamma (NSG) mice were randomized into three groups to investigate their therapeutic effect. After induction of MDA-MB-231, the NSG mice were monitored daily for well-being and tumor growth. Once tumor size was approximately one millimeter, the CD8+ T cells and tumoractivated moDCs pulsed CD8+ T cells were injected intravenously twice a week for three weeks. A month after the last treatment, all NSG mice were terminated and tumor prognosis was evaluated by performing histological analysis on the mammary fat pads and livers. Interferon (IFN)-g , interleukin (IL)-4, IL-10 and IL-17 levels were evaluated in the serum using luminex cytokine array and T-bet, GATA-3, Foxp3, ROR-gamma t gene expression in the mammary fat pad and the liver were measured using quantitative real-time polymerase chain reaction (qRT-PCR).
Results: Tumor-bearing NSG mice treated with CD8+ T cells and tumor-activated moDCs pulsed CD8+ T cells significantly reduced tumor necrosis in the liver but not in the mammary fat pad compared to untreated tumorbearing NSG mice. No difference was seen in the secretion levels of IFN-g , IL-4, IL-10, and IL-17 in the serum of untreated and treated tumor-bearing NSG mice before and after treatment. Mammary fat pad and liver isolated from the tumor-bearing NSG mice treated with CD8+ T cells and tumor-activated moDCs pulsed CD8+ T cells showed increased T-bet gene expression but reduced GATA-3, Foxp3, and RORgamma t gene expression.
Conclusion: The current study indicated that tumoractivated moDCs pulsed CD8+ T cells treated mice showed better outcomes in reducing tumor necrosis compared to CD8+ T cells, which is supported by increased anti-tumor related gene expression and reduced pro-tumor related gene expression in the mammary fat pads and livers of tumor-bearing NSG mice.