Soluble CD160 augments cytokine secretion and cytolytic activity by tumor-specific CD8-T cells in vitro

Aim/Background

CD160 is a new co-inhibitory molecular, expression of which is generally associated with T cells dysfunction in chronic viral infections and is considered as an exhaustion marker of virus-specific CD8⁺ T cells. However, its contribution to tumor-specific CD8⁺ T cells impairment remains unclear. Here, we sought to decipher its regulation on tumor-specific CD8⁺ T cells function.

Methods

We separated CD8⁺ T cells from splenocytes of tumor-bearing mice with immunomagnetic beads and detected expression of CD160 and HVEM by flow cytometry. We expressed the extracellular domain of murine CD160 (soluble form of CD160), which could block the interaction between CD160 and HVEM, the ligand of CD160, by binding HVEM. Then, the activity of proliferation and cytolytsis and secretion of cytokines by CD8⁺ T cells were measured.

Results

We found the evaluation of CD160 and HVEM expression on CD8⁺ T cells from tumor-bearing mice. Expression of CD160 defined a relatively decreased immune function subset of CD8⁺ T cells, with lower proliferation and cytotoxicity activity and less cytokine production. Soluble CD160 augments CD8⁺ T cells activation by DCs loaded with specific tumor antigen, resulting in increased IFN-ɣ, IL-2 and TNF-α secretion and enhanced cytolysis against target tumor cells.

Conclusions

We thus conclude that up-regulated expression of CD160 is related to CD8⁺T cells dysfunction and blocking the CD160-HVEM interaction with soluble CD160 enhances immunological activity and function of tumor-specific CD8⁺T cells in vitro.

Clinical trial identification

Disclosure

All authors have declared no conflicts of interest.