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Poster session 01

88P - DNA-methylome derived epigenetic fingerprint as an immunophenotype indicator prompts durable clinical immunotherapeutic benefits in head and neck squamous cell carcinoma

Date

10 Sep 2022

Session

Poster session 01

Topics

Immunotherapy

Tumour Site

Head and Neck Cancers

Presenters

Rui Li

Citation

Annals of Oncology (2022) 33 (suppl_7): S27-S54. 10.1016/annonc/annonc1037

Authors

R. Li1, X. Tang1, Y. Wang1, X. Wen1, X. Ren2, R. Lv1, F. Zhao1

Author affiliations

  • 1 Department Of Radiation Oncology, Nanfang Hospital of Southern Medical University, 510515 - Guangzhou/CN
  • 2 Sun Yat-sen University, Guangdong Provincial Key Laboratory Of Stomatology, Hospital of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, Guangzhou/CN
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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.

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