Abstract 88P
Background
Cancer immunotherapy has provided durable responses and improved survival in a subset of patients with head and neck squamous cell carcinoma (HNSC). Epigenetic mechanisms played critical roles not only in initiation and progression of HNSC, but also in the activation and effector functions of immune cells.
Methods
We firstly distinguished the immune ‘hot’ and ‘cold’ immunophenotypes of HNSC based on five immune expression signatures in a training cohort of 493 HNSC samples from the Cancer Genome Atlas. We correlated the immunophenotypes with DNA methylation level, then used Boruta and random forest algorithm to generate a methylation-based classifier. We validated the prognostic accuracy and immune cell infiltration level of this methylation classifier in three independent datasets containing 132 HNSC samples. Moreover, its predictive value for immunotherapy was then analyzed in a lung adenocarcinoma (LUAD) dataset.
Results
HNSC classified as ‘hot’ immunophenotype had higher immunoactivity and better overall survival (p=0.00055) than ‘cold’ tumors. At the epigenome level, we observed that distinct DNA methylation patterns between immunophenotypes were closely associated with HNSC tumorigenesis as well as infiltration of functional immune cells. We identified 311 immunophenotype-related methylated CpG sites from The TCGA HNSC dataset. An immunophenotype-related methylated signatures (IPMS) consisted of 7 CpG sites were generated to classify patients into ‘Hot’ and ‘Cold’ immunophenotypes. The robustness of the IPMS was verified in the validation datasets. Moreover, it was also validated as a well-performed classifier (p = 0.027) for predicting durable clinical benefits in LUAD patients who received anti-PD-1/PD-L1 immunotherapy.
Conclusions
The IPMS is a reliable epigenome prognostic tool in clinical tumor immunophenotyping. It has the potential to guide immunotherapeutic strategies and may facilitate the development of personalized epigenetic anticancer approaches for different HNSC subgroups.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
The National Natural Science Foundation of China, the Natural Science Foundation of Guangdong Province.
Disclosure
All authors have declared no conflicts of interest.