MAP1LC3C repression reduces CIITA- and HLA class II expression in non-small cell lung cancer

In the last decade, advancements in understanding the genetic landscape of lung squamous cell carcinoma (LUSC) have significantly impacted therapy development. Immune checkpoint inhibitors (ICI) have shown great promise, improving overall and progression-free survival in approximately 25% of the patients. However, challenges remain, such as the lack of predictive biomarkers, difficulties in patient stratification, and identifying mechanisms that cancers use to become immune-resistant ("immune-cold"). Analysis of TCGA datasets reveals reduced MAP1LC3C expression in cancer. Further analysis indicates that low MAP1LC3C is associated with reduced CIITA and HLA expression and with decreased immune cell infiltration. In tumor cells, silencing MAP1LC3C inhibits CIITA expression and suppresses HLA class II production. These findings suggest that cancer cells are selected for low MAP1LC3C expression to evade efficient immune responses.