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% of
the cases. PD-1 inhibitor is an antibody used in immunotherapy to treat cancer. Previous studies have reported that
the PD-1 inhibitor can block the PD-1/PD-L1 binding and help the immune system recognize and attack tumors. The
PI3K/AKT signaling pathway is an important target of the PD-1 downstream pathway. This paper studies the effects of
PD-1 inhibitor Pembrolizumab on the activation of the PI3K/AKT pathway in vivo. In this study, A549 cell line will
be 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 activation
of tumor cells and CD4 T cells. This paper investigates whether or not PD-1 inhibitor would effectively block the
PI3K/AKT pathway and increase T cell proliferation. The result of this study will explore the blocking mechanism of
Pembrolizumab on PI3K/AKT pathway. Future studies should focus on the acquired resistance caused by mutations and
its effects on PD-1 inhibitor treatment with PI3K/AKT pathway activation as the biomarker.