Canine diffuse large b-cell lymphoma downregulates the activity of CD8 + T-cells through tumor-derived extracellular vesicles
Journal
Cancer Cell International
Journal Volume
23
Journal Issue
1
Date Issued
2023-12-01
Author(s)
Weng, Hsin Pei
Ke, Chiao Hsu
Tung, Chun Wei
Tani, Akiyoshi
Wang, Yu Shan
Han, Winston
Liao, Chi Hsun
Tomiyasu, Hirotaka
Abstract
Background: Tumor-derived extracellular vesicles (EVs) have been proposed as the essential mediator between host immunity and cancer development. These EVs conduct cellular communication to facilitate tumor growth, enable invasion and metastasis, and shape the favorable tumor microenvironment. Lymphoma is one of the most common hematological malignancies in humans and dogs. Effective T-cell responses are required for the control of these malignancies. However, the immune crosstalk between CD8 + T-cells, which dominates anti-tumor responses, and canine lymphoma has rarely been described. Methods: This study investigates the immune manipulating effects of EVs, produced from the clinical cases and cell line of canine B cell lymphoma, on CD8 + T-cells isolated from canine donors. Results: Lymphoma-derived EVs lead to the apoptosis of CD8 + T-cells. Furthermore, EVs trigger the overexpression of CTLA-4 on CD8 + T-cells, which indicates that EV blockade could serve as a potential therapeutic strategy for lymphoma patients. Notably, EVs transform the CD8 + T-cells into regulatory phenotypes by upregulating their PD-1, PD-L1, and FoxP3 mRNA expression. The regulatory CD8 + T-cells secret the panel of inhibitory cytokines and angiogenic factors and thus create a pro-tumorigenic microenvironment. Conclusion: In summary, the current study demonstrated that the EVs derived from canine B cell lymphoma impaired the anti-tumor activity of CD8 + T-cells and manipulated the possible induction of regulatory CD8 + T-cells to fail the activation of host cellular immunity.
Subjects
CD8 + T-cell | CTLA-4 blockade | Diffuse large B-cell lymphoma | Extracellular vesicles | Immune suppression
SDGs
Type
journal article