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

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.

Clustering and machine learning-based integration identify cancer associated fibroblasts genes’ signature in head and neck squamous cell carcinoma

“…In addition, compared to the conventional tools such as age, gender, stage and HPV status for evaluating clinical outcomes, the risk score signature worked independently of these factors and had significantly superior efficiency in predicting prognosis in training and validation cohorts. We also reviewed previous published HNSCC-related risk models which including different genes’ combination ( Liu et al, 2020 ; Li et al, 2021b ; He et al, 2021 ; Wang et al, 2022a ; Huang et al, 2022b ; Wang et al, 2022b ; Chen et al, 2022 ; Chi et al, 2022 ; Du et al, 2022 ; Han et al, 2022 ; Peng et al, 2022 ), among these, none of them presented better AUC value performance than our model. Therefore, our risk score signature could be a promising surrogate for evaluating the prognosis of HNSCC in clinical practice.…”

Gene and Genetic Studies of Tumor Microenvironment

“…Interestingly, in our cohort, FAM135B mutations occurred only in LCLC, with a 35% mutation rate, suggesting that the mutation may be specific to LCLC compared to LCNEC. It has been reported to have high mutation rates in other lung cancers such as LUSC (Xie et al, 2021) and SCLC (Hu et al, 2019;Wang et al, Frontiers in Genetics frontiersin.org 2019). Esophageal squamous cell carcinoma has been shown to strongly express FAM135B with poor prognosis and silencing FAM135B increases radiosensitivity (Bi et al, 2021;Dong et al, 2021), but there is little evidence to support mutation as the underlying cause of elevated expression.…”