Abstract LB228: PD-L1/PD-1 and arsenic lung tumorigenesis

Abstract

Abstract Chronic exposure of environmental arsenic promotes lung cancer. Emerging evidence indicates that compromised host immunity, particularly T cell anti-tumor immunity, may play a critical role in cancer development. However, there is a knowledge gap in terms of the effects of arsenic exposure on T cell anti-tumor immunity and how that may contribute to arsenic lung carcinogenicity. Immunosuppression has been known as a risk factor for many types of cancer, including lung cancer. The development of cancer indicates a success of immunosuppression and escape of cancer cells from host anti-tumor immunity in which T cells are the major component. The anti-tumor immunity is mainly executed by CD8 cytotoxic T cells through their anti-tumor effector function. A/J mice are naturally sensitive to pulmonary carcinogens and prone to develop spontaneous lung tumors later in life and have been frequently used as an animal model for lung tumorigenesis research. Chronic arsenic administration through drinking water has been shown to enhance tumor formation in the lungs of A/J mice. In the current study, using this mouse model we determined that prolonged arsenic exposure up-regulated PD-1/PD-L1, inhibited T cell antitumor function and enhanced lung tumor formation, while inhibition of PD-1/PD-L1 restored T cell anti-tumor effector function and mitigated arsenic-enhanced lung tumorigenesis. In addition, inhibition of PD-1/PD-L1 could be a preventive approach to mitigate tumorigenic action of chronic arsenic exposure. Citation Format: Wenhua Xu, Gang Chen. PD-L1/PD-1 and arsenic lung tumorigenesis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr LB228.