6P - Expression of PD-L1 in lung cancer cells regulates Treg cell differentiation

Date 15 April 2016
Event European Lung Cancer Conference 2016 (ELCC) 2016
Session Poster lunch
Topics Thoracic malignancies
Translational Research
Basic Principles in the Management and Treatment (of cancer)
Presenter Minhua Shi
Citation Journal of Thoracic Oncology (2016) 11 (supplement 4): S57-S166. S1556-0864(16)X0004-4
Authors M. Shi
  • Respiratory Diseases, 2nd Affiliated Hospital Suzhou (Soochow) University, 215004 - Suzhou/CN

Abstract

Background

Both regulatory T cells (Tregs) and the programmed cell death-1 (PD-1)/PD-L1 pathway play important roles in lung cancer pathogenesis; however, the association between these two factors remains poorly understood. Hereby, we examined PD-L1 expression in lung cancer cells, and analyzed its effect on induced Treg cells.

Methods

PD-L1 expression was studied on lung cancer cells by flow cytometry. Peripheral blood mononuclear cells (PBMC) were isolated from a healthy volunteer, and then immune magnetic beads were used to sort out human peripheral blood T lymphocyte and detect separation purity. Plant blood agglutinin (PHA) was used to stimulate the peripheral blood T lymphocyte. Activated T cells were co-cultured with lung cancer cells which expressed the highest level of PD-L1, to which transforming growth factor-β (TGF-beta) was added to block PD-L1 type antibody. Then the degree of Treg cell differentiation was detected.

Results

The expression of B7-H1 was detected in four human lung cancer cell lines using flow cytometry. We found that the membrane expression level of PD-L1 was the highest on the A549 cells. After PHA stimulation, T lymphocyte proliferation was activated. Then the activated T lymphocytes and A549 cells were co-cultured. Only a small part of T lymphocytes differentiated into Treg cells in the absence of TGF-beta. However, in the presence of TGF-beta, when adding anti-PD-L1 monoclonal antibody, the differentiation of T lymphocytes into Treg cells was reduced. When TGF-beta and PD-L1 existed at the same time, the highest degree of T lymphocyte differentiation into Treg cells were observed.

Conclusions

Expression of PD-L1 in lung cancer cells can coordinate TGF-beta to induce human peripheral blood T lymphocyte differentiation to Treg cells. Its role in immuno­suppression may promote the occurrence and development of tumors.

Clinical trial identification

Legal entity responsible for the study

The Ethics Committee of The Second Affiliated Hospital of Soochow University

Funding

The National Natural Science Foundation of China (No. 81272610)

Disclosure

All authors have declared no conflicts of interest.