Abstract
The major histocompatibility complex class I (MHC-I) transactivator, nucleotide binding oligomerization domain-like receptor family caspase recruitment domain containing 5 (NLRC5), serves as a target for immune evasion in many cancers, including endometrial cancer (EC). An inhibition of autophagy can contribute to immunotherapy by assisting the MHC-I-mediated antigen presentation in cancer. However, the underlying mechanism for autophagy-regulated MHC-I in EC remains unclear. In this study, we found that autophagy was upregulated in EC tissues when compared to that in normal endometrial tissues. MHC I and NLRC5 expressions were lower in EC endometrium than in normal endometrium. Autophagy inhibited the MHC-I genes expression in vitro. Furthermore, a negative correlation was found between NLRC5 and LC3 levels, and LC3 interacted with NLRC5 to inhibit NLRC5-mediated MHC-I antigen presentation pathway in vitro and in vivo. Thus, our findings demonstrated that an upregulation of LC3 in EC patients may contribute to tumor immune escape by restricting the NLRC5-mediated MHC-I antigen presentation pathway, signifying inhibiting LC3 and promoting NLRC5 may be a promising immunotherapy strategy in the management of EC.