Regulation of the process of antigen presentation in cancer cells under oxidative stress conditions

Rashed Alhammad, Sasiprapa Khunchai, Nopprarat Tongmuang, Thawornchai Limjindaporn, Pa-thai Yenchitsomanus, Marija Krstic-Demonacos, Costas Demonacos

Research output: Contribution to conferenceAbstractpeer-review

Abstract

Efficient elimination of tumour cells by the immune system requires recognition of tumour cells and in this process antigen presentation is a very important step. Cancer cells use several mechanisms to evade immunosurveillance including defects in antigen presentation due to reduced expression or instability of the major histocompatibility complex (MHC) or presentation of “inappropriate” antigen by cancer cells. Elevated oxidative stress and high levels of reactive oxygen species (ROS) which are common characteristics of cancer cells affect antigen presentation by regulating the expression or the type (classical versus non classical) as well as the assembly of MHC class I molecules. The effects of ROS on MHC class I are mediated by endoplasmic reticulum proteins such as the Protein Disulphide Isomerase (PDI) or prolyl 4-hydroxylase subunit beta (P4HB) and the Endoplasmic Reticulum Oxidoreductase 1 alpha (ERO1A). We hypothesized that by modulating the cellular levels and the function of P4HB it would be possible to control the process of antigen presentation in breast cancer cells and tested this hypothesis following the cellular levels of different MHC class I isoforms in these cells in vitro. Altered ROS levels were generated in breast cancer cells by beta-estradiol, interferon gamma and etoposide treatment and the PDI and MHC class I cellular levels were followed in treated and untreated cells. To confirm that alterations of MHC class I cellular levels were associated with P4HB function the gene expression of this PDI family member was silenced using siRNA and the MHC class I surface levels were followed in IFN-γ and etoposide treated breast cancer cells. In addition, the levels of expression of microRNAs (miRNAs) found by in silico methods to target P4HB were followed in β-estradiol, IFN-γ and etoposide treated breast cancer cells. Our preliminary unpublished data indicated that P4HB regulated the plasma membrane levels of the classical and the non-classical MHC class I in breast cancer cells in a manner dependent on the cellular levels of ROS.
Original languageEnglish
Publication statusPublished - 2018
EventInternational Conference on Cancer Immunotherapy 2018 - MR 211 & 212 BITEC, Bangkok, Thailand, Bangkok, Thailand
Duration: 13 Sept 201814 Sept 2018

Conference

ConferenceInternational Conference on Cancer Immunotherapy 2018
Country/TerritoryThailand
CityBangkok
Period13/09/1814/09/18

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