Autophagy subtypes characterization identifies immune phenotypes and immunotherapy response in head and neck squamous cell carcinoma (HNSCC)

Abstract

Background Autophagy degraded and recycled cytoplasmic components to maintain cellular homeostasis under stress conditions, which was recognized as double-edged sword in oncogenesis and novel target in cancer treatment. However, comprehensive analysis of the relationship between autophagy regulation and immunity has not been reported yet. Methods Unsupervised consensus clustering algorithm was used to identify autophagy regulation patterns. LASSO cox regression algorithm was used to build a scoring system (ATGscore) to represent the individual autophagy regulation pattern. Then integrated analysis of autophagy regulation patterns and ATGscore was performed. Results We have successful depicted five autophagy regulation patterns and established a scoring system (ATGscore) to represent it, which was shown to be significantly correlated with TIME infiltration, immune phenotypes, molecular subtypes, and genetic variation, etc. in 1165 head and neck squamous cell carcinoma (HNSCC) patients. Moreover, ATGscore was an independent prognostic factor and potent predictor for clinical response to immune-checkpoint inhibitors (ICIs) targeting immunotherapy. Conclusions Understanding the molecular characteristics of autophagy regulation patterns in HNSCC could help us to depict the underlying mechanism of tumour immunity and lay a solid foundation on combination of autophagy targeting therapies and immunotherapies for clinical application in HNSCC.