Tumor-Infiltrating CD4(+) Central Memory T Cells Correlated with Favorable Prognosis in Oral Squamous Cell Carcinoma

Objective: Oral squamous cell carcinoma (OSCC) is the most frequent oral malignancy with a poor prognosis, in which tumor-infiltrating immune cells may play a critical role. Therefore, our study aims to screen potential immune cells and immune-related genes for predicting OSCC prognosis. Methods: A total of 310 OSCC patients with full transcriptional data and clinical characteristics were extracted from the TCGA database. Then, we obtained their abundance of tumor-infiltrating immune cells on TIMER 2.0 and analyzed them using xCell method. Univariate and multivariate Cox regressions were applied successively to identify the immune cells associated with overall survival of OSCC patients. Furthermore, we screened the prognostic genes that related to the identified immune cells and validated their expressions by immunohistochemistry. Results: CD4(+) central memory T (T-CM) cell was recognized as the sole independent immune cell correlated with OSCC prognosis (p = 0.0085). A novel nomogram based on CD4(+) T-CM cell abundance was established for predicting the prognosis of OSCC patients, with calibration plots showing good performance for 1-, 3-, 5-year overall survival. Thirty-four related prognostic genes were screened according to the differential abundance of CD4(+) T-CM cell infiltration. In immunohistochemistry analysis, DEFB1 showed a significant positive relationship with the density of CD4(+ )T(CM) cells (p = 0.0075). Conclusion: CD4(+ )central memory T cell was proposed as an independent prognostic biomarker for OSCC patients. DEFB1 might positively regulate the abundance of tumor-infiltrating CD4(+) T-CM cells, thus improving OSCC prognosis. Our findings may provide a new insight into better prognosis prediction and precise medicine for OSCC.

Automated summary

This study aimed to screen immune cells and genes related to the prognosis of oral squamous cell carcinoma (OSCC). Through the analysis of data from the TCGA database, CD4(+) central memory T cells were identified as the only independent immune cell associated with the prognosis of OSCC. A prognostic prediction model based on the abundance of CD4(+) T cells was established. In addition, 34 prognostic genes related to the infiltration of CD4(+) central memory T cells were screened, and DEFB1 was found to potentially regulate the abundance of these cells and improve the prognosis of OSCC.