Abstract
Endometrial cancer (EC), the most common gynecological cancer, is usually resistant to chemotherapy when the EC patients are advanced or recurrent. Immunotherapy is a promising approach to treat advanced or recurrent EC patients. The innate immune molecule NLRC5 (NLR family CARD domain containing 5) is a major histocompatibility complex class I (MHC-I) transactivator, which is intimately associated with tumor antigen presentation. The absence of NLRC5 expression in cancer results in immune evasion and resistance to immunotherapy. Previously, we found that NLRC5 was downregulated in EC patients, suggesting that NLRC5 is a target for immune evasion in EC. In our recent study, we indicated that autophagy inhibits NLRC5 and NLRC5-mediated MHC-I gene expression in vitro. Of special note is that autophagy protein MAP1LC3/LC3 interacts with NLRC5 to inhibit the NLRC5-mediated MHC-I antigen presentation pathway in vitro and in vivo, which presents a novel mechanism underlying NLRC5-mediated immune evasion by autophagy in EC. Our results reveal a previously unknown mechanism of autophagy protein LC3 in the regulation of NLRC5-mediated MHC-I antigen presentation in EC, and highlight a potential immunotherapy approach in EC patients by inhibiting LC3 and promoting NLRC5.