NLRC5 regulates expression of MHC-I and provides a target for anti-tumor immunity in transmissible cancers.

ABSTRACT:

Purpose

Downregulation of MHC class I (MHC-I) is a common immune evasion strategy of many cancers. Similarly, two allogeneic clonal transmissible cancers have killed thousands of wild Tasmanian devils (Sarcophilus harrisii) and also modulate MHC-I expression to evade anti-cancer and allograft responses. IFNG treatment restores MHC-I expression on devil facial tumor (DFT) cells but is insufficient to control tumor growth. Transcriptional co-activator NLRC5 is a master regulator of MHC-I in humans and mice but its role in transmissible cancers remains unknown. In this study, we explored the regulation and role of MHC-I in these unique genetically mis-matched tumors.

Methods

We used transcriptome and flow cytometric analyses to determine how MHC-I shapes allogeneic and anti-tum

SUBMITTER: Ong CEB 

PROVIDER: S-EPMC8017436 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature