RESUMO
Background: The heterogeneous crosstalk between tumor cells and other cells in their microenvironment means a notable difference in clinical outcomes of head and neck squamous cell carcinoma (HNSCC). CD8+ T cells and macrophages are effector factors of the immune system, which have direct killing and phagocytosis effects on tumor cells. How the evolution of their role in the tumor microenvironment influences patients clinically remains a mystery. This study aims to investigate the complex communication networks in the HNSCC tumor immune microenvironment, elucidate the interactions between immune cells and tumors, and establish prognostic risk model. Methods: 20 HNSCC samples single-cell rna sequencing (scRNA-seq) data and bulk rna-seq data were derived from public databases. The "cellchat" R package was used to identify cell-to-cell communication networks and prognostic related genes, and then cell-cell communication (ccc) molecular subtypes were constructed by unsupervised clustering. Kaplan-Meier(K-M) survival analysis, clinical characteristics analysis, immune microenvironment analysis, immune cell infiltration analysis and CD8+T cell differentiation correlation analysis were performed. Finally, the ccc gene signature including APP, ALCAM, IL6, IL10 and CD6 was constructed based on univariate Cox analysis and multivariate Cox regression. Kaplan-Meier analysis and time-dependent receiver operating characteristic (ROC) analysis were used to evaluate the model in the train group and the validation group, respectively. Results: With CD8+T cells from naive to exhaustion state, significantly decreased expression of protective factor (CD6 gene) is associated with poorer prognosis in patients with HNSCC. The role of macrophages in the tumor microenvironment has been identified as tumor-associated macrophage (TAM), which can promote tumor proliferation and help tumor cells provide more nutrients and channels to facilitate tumor cell invasion and metastasis. In addition, based on the strength of all ccc in the tumor microenvironment, we identified five prognostic ccc gene signatures (cccgs), which were identified as independent prognostic factors by univariate and multivariate analysis. The predictive power of cccgs was well demonstrated in different clinical groups in train and test cohorts. Conclusion: Our study highlights the propensity for crosstalk between tumors and other cells and developed a novel signature on the basis of a strong association gene for cell communication that has a powerful ability to predict prognosis and immunotherapy response in patients with HNSCC. This may provide some guidance for developing diagnostic biomarkers for risk stratification and therapeutic targets for new therapeutic strategies.
RESUMO
BACKGROUND: As one of the core aging processes, cellular senescence is associated with tumorigenesis, growth, and immune modulation in cancers. Nevertheless, the prognosis of senescence-associated genes (SAGs) signature in head and neck squamous cell carcinoma (HNSCC) remains to be further evaluated. METHODS: The transcriptome and corresponding clinical datasets of SAGs in patients with HNSCC were downloaded from public databases. A new prognostic SAGs signature was established with least absolute shrinkage and selection operator discussion. Patients with HNSCC were fallen into two risk groups based on each sample's risk mark and the cutoff point. The survival analysis was extended to determine the predictive accuracy of the SAGs signature. Furthermore, the evaluation of SAGs signature was made according to clinicopathological characteristics, survival state, the infiltration of inflammatory cells, and efficacy of immunotherapy. RESULTS: 41 SAGs were recognized and adopted to establish the forecast signature. The survival analysis indicated that patients with HNSCC in the high-senescent score group had significantly reduced overall survival compared with those in the low-senescent score group. It was certified that the risk score of SAGs signature was a separate predicting agent for HNSCC applying Cox regression analysis. According to functional analysis, some immune-associated pathways were increased in the low-senescent score group significantly. High-senescent score group was correlated with poor clinicopathological characteristics, given less the infiltration of inflammatory cells state and worse immunotherapeutic effect. CONCLUSION: A new SAG signature predicting result and response to immunotherapy of HNSCC was identified. Cellular senescence may be a hidden target for HNSCC.
