A Tumor-Infiltration CD8+ T Cell-Based Gene Signature for Facilitating the Prognosis and Estimation of Immunization Responses in HPV+ Head and Neck Squamous Cell Cancer

• Main Authors: Yingning Wu, Lingzhang Meng, Kai Cai, Jingjie Zhao, Siyuan He, Jiajia Shen, Qiuju Wei, Zechen Wang, Suren Sooranna, Hengguo Li, Jian Song
• Format: Article
• Language: English
• Published: Frontiers Media S.A. 2021-09-01
• Series: Frontiers in Oncology
• Subjects: CD8+ T cells; HPV; immunization-correlated genes; immunization-correlated therapy; differentially expressed genes; predicted prognosis
• Online Access: https://www.frontiersin.org/articles/10.3389/fonc.2021.749398/full

BackgroundCD8+ T cells, which play a vital role in response to adaptive immunity, are closely related to the immunization responses to kill tumor cells. Understanding the effects exerted by tumor-infiltrated CD8+ T cells in HPV+ and HPV- head and neck squamous cell carcinoma (HNSCC) patients is critical for predicting their prognosis as well as their responses towards immunization-related therapy.Materials and MethodsHNSCC single cell transcriptome was used to screen for differentially expressed genes (DEGs) based on CD8+ T cells. A gene signature associated with CD8+ T cells was built and verified with the cancer genome atlas dataset with a view to predicting the prognosis of HNSCC patients. Risk scores were calculated for HNSCC cases and categorized into either high- or low-risk cohorts. The prognosis-correlated data of the risk scores were analyzed by using Kaplan-Meier survival curves and multi-variate Cox regression plots. In addition, the possibility of using the genetic profiles to predict responses toward immunization-related therapy was explored.ResultsFrom the DEGs screened from the sequencing of single-cell RNA, a gene signature of 4 genes (ACAP1, ANKRD28, C12orf75, and M6PR) were identified. It was seen that these genes could predict overall survival in HPV+ HNSCC patients. In addition, high- and low-risk HPV+ HNSCC patients showed marked differences in their CD8+ T-cell infiltration due to immunization when clinical characteristics were taken into consideration. This correlated with their immunization therapy responses.ConclusionsOur work provides insights into explaining the restricted responses of current immunization checkpoint inhibiting substances in HPV+ HNSCC patients. A novel genetic signature to predict the prognosis and immunization-correlated therapeutic responses is presented. This will provide potential new therapeutic opportunities for HPV+ HNSCC patients.