Exosomal PD-L1 promotes tumor growth through immune escape in non-small cell lung cancer.

Abstract

Programmed cell death protein-1/programmed cell death ligand-1 (PD-1/PD-L1) pathway blockade is a promising new cancer therapy. Although PD-1/PD-L1 treatment has yielded clinical benefits in several types of cancer, further studies are required to clarify predictive biomarkers for drug efficacy and to understand the fundamental mechanism of PD-1/PD-L1 interaction between host and tumor cells. Here, we show that exosomes derived from lung cancer cells express PD-L1 and play a role in immune escape by reducing T-cell activity and promoting tumor growth. The abundance of PD-L1 on exosomes represented the quantity of PD-L1 expression on cell surfaces. Exosomes containing PD-L1 inhibited interferon-gamma (IFN-γ) secretion by Jurkat T cells. IFN-γ secretion was restored by PD-L1 knockout or masking on the exosomes. Both forced expression of PD-L1 on cells without PD-L1 and treatment with exosomes containing PD-L1 enhanced tumor growth in vivo. PD-L1 was present on exosomes isolated from the plasma of patients with non-small cell lung cancer, and its abundance in exosomes was correlated with PD-L1 positivity in tumor tissues. Exosomes can impair immune functions by reducing cytokine production and inducing apoptosis in CD8+ T cells. Our findings indicate that tumor-derived exosomes expressing PD-L1 may be an important mediator of tumor immune escape.

• Authors: Dong Ha Kim, HyeongRyul Kim, Yun Jung Choi, Seon Ye Kim, Jung-Eun Lee, Ki Jung Sung, Young Hoon Sung, Chan-Gi Pack, Min-Kyo Jung, Buhm Han, Kunhee Kim, Woo Sung Kim, Soo Jeong Nam, Chang-Min Choi, Miyong Yun, Jae Cheol Lee, Jin Kyung Rho
• Journal: Experimental & molecular medicine (Exp Mol Med) Vol. 51 Issue 8 Pg. 1-13 (08 09 2019) ISSN: 2092-6413 [Electronic] United States
• PMID: 31399559 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• B7-H1 Antigen
• CD274 protein, human

Topics

• A549 Cells
• Animals
• B7-H1 Antigen (genetics, metabolism, physiology)
• CD8-Positive T-Lymphocytes (immunology)
• Carcinoma, Non-Small-Cell Lung (genetics, immunology, pathology)
• Cell Proliferation (genetics)
• Cells, Cultured
• Exosomes (genetics, metabolism, pathology)
• HEK293 Cells
• Heterografts
• Humans
• Jurkat Cells
• Lung Neoplasms (genetics, immunology, pathology)
• Male
• Mice
• Mice, Inbred C57BL
• Tumor Escape (genetics)
• Tumor Microenvironment (genetics, immunology)