Necroptosis is Related to Anti-PD-1 Treatment Response and Influences the Tumor Microenvironment in Head and Neck Squamous Cell Carcinoma

Qiwei Wang; Fang Wang; Yinan Zhao; Guolin Tan

doi:10.3389/fgene.2022.862143

Necroptosis is Related to Anti-PD-1 Treatment Response and Influences the Tumor Microenvironment in Head and Neck Squamous Cell Carcinoma

Front Genet. 2022 May 25:13:862143. doi: 10.3389/fgene.2022.862143. eCollection 2022.

Authors

Qiwei Wang¹, Fang Wang², Yinan Zhao³, Guolin Tan¹

Affiliations

¹ Department Otolaryngology Head and Neck Surgery, Third Xiangya Hospital, Central South University, Changsha, China.
² Otorhinolaryngology, Klinikum Rechts der Isar of the Technical University of Munich, Munich, Germany.
³ Xiangya School of Nursing, Central South University, Changsha, China.

Abstract

The latest research suggesting that necroptosis plays a vital role in immune response. However, the influence of necroptosis on tumor microenvironment (TME) remodeling and immunotherapy is still unclear. We analyzed the variations in the expression of 26 necroptosis-related molecules in HNSCC and the influence of genome changes. We investigated HNSCC samples and determined that there are two necroptosis phenotypes in HNSCC cancer, and there are significant differences in cell infiltration characteristics and survival in different necroptosis phenotypes. We used the single-sample gene set enrichment analysis to measure the level of necroptosis in patients with NecroticScore, we confirmed that the NecroticScore can predict the prognosis of HNSCC patients and the response to immunotherapy. Patients with a high NecroticScore are more sensitive to immunotherapy and have a better prognosis. Our study suggests a significant correlation between the expression imbalance of necroptosis-related molecules and suggests necroptosis plays an important role in modeling the TME. In addition, we construct a risk prediction model which could stratify patients with HNSCC and predict patient prognosis according to this necroptosis-related molecules. In conclusion, evaluating necroptosis modification patterns contributes to enhancing our understanding of TME and can guide more effective immunotherapy strategies.

Keywords: PD1 = programmed cell death protein 1; head and necek squamous cell carcinoma; immunephenotype; necroptosis; the tumor immune microenvironment.