Investigating ERO1α, IDO1 and MHC Class I : potential proteins that can be manipulated to change the tumour microenvironment from ‘cold’ to ‘hot’

• Main Author: Peck, Jia Yi
• Other Authors: Sze Siu Kwan
• Format: Final Year Project
• Language: English
• Published: Nanyang Technological University 2020
• Subjects: Science::Biological sciences
• Online Access: https://hdl.handle.net/10356/143295
• Institution: Nanyang Technological University

ERO1α, a cancer-associated protein, and IDO1, an immunomodulatory enzyme, have been shown to be associated with the expression of MHC Class I proteins. Previous study done by our lab that showed ERO1α association with hypoxic tumour progression, also had preliminary data indicating that under hypoxia, there is an increase in amino acid tryptophan catabolism by IDO1. However, there is still no direct linkage found between these 3 proteins, which could be potentially manipulated to turn the tumour microenvironment (TME) from ‘cold’ to ‘hot’. In this study, we investigated the effects of inhibiting ERO1α and IDO1 on MHC Class I and ERO1α expression. We discovered that MHC Class I expression increased while ERO1α expression decreased upon ERO1α inhibition and IDO1 inhibition. IDO1 expression also increased under hypoxia. SILAC proteomics method was used to gain insight on proteins upregulated and downregulated after IDO1 inhibition. Results showed that proteins involved in immune activation were upregulated, particularly immunoglobulins. These results provide insights on potential interactions between ERO1α, IDO1, and MHC Class I in the TME which could be potential immunotherapy targets in the future.