Effect of PD-1 Inhibitor on PI3K/AKT Pathway in Tumor Cell and TCell Activity in Non-small Cell lung Cancer (NSCLC)

Abstract

Lung cancer is one of the most lethal cancers around the world and non-small cell lung cancer takes up about 85% ofthe cases. PD-1 inhibitor is an antibody used in immunotherapy to treat cancer. Previous studies have reported thatthe PD-1 inhibitor can block the PD-1/PD-L1 binding and help the immune system recognize and attack tumors. ThePI3K/AKT signaling pathway is an important target of the PD-1 downstream pathway. This paper studies the effects ofPD-1 inhibitor Pembrolizumab on the activation of the PI3K/AKT pathway in vivo. In this study, A549 cell line willbe used as the non-small cell lung cancer model. The immune-deficient mice will be injected with Keytruda, saline(negative control) or Taxol (positive control). Flow cytometry and Western Blot will be used to measure the activationof tumor cells and CD4 T cells. This paper investigates whether or not PD-1 inhibitor would effectively block thePI3K/AKT pathway and increase T cell proliferation. The result of this study will explore the blocking mechanism ofPembrolizumab on PI3K/AKT pathway. Future studies should focus on the acquired resistance caused by mutations andits effects on PD-1 inhibitor treatment with PI3K/AKT pathway activation as the biomarker.