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

Abstract

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.

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“…Central memory CD8 + T cells have been shown to exert strong antitumor activity and have been associated with a better prognosis in cancer patients ( 32 ). Central memory CD4 + T cells have also been proposed as an independent prognostic biomarker of oral squamous cell carcinoma ( 33 ). Natural killer cells not only exert antitumor effects via direct cytolytic activity but also indirectly exert antitumor effects through cytokine production ( 34 ).…”

Network pharmacology and bioinformatics analysis on the underlying mechanisms of baicalein against oral squamous cell carcinoma

“…43 The complex cross-talk between cancer cells and immune cells plays an important role in the tumor development and progress. 44 Wu and colleagues 45 recently performed Cox regressions to identify the immune cells associated with OSCC survival. The results revealed that CD4 + central memory T as an independent immune cell was significantly associated with the prognosis of OSCC.…”

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“…In this study, we also found that a low central memory CD4 T cell expression level was associated with longer PFS in the sintilimab arm. The function of central memory CD4 T cells in the tumor microenvironment remains unclear [ 41 , 42 ]. However, it was reported that transforming growth factor‐β could induce CD4+CD62L+ central memory T cells to differentiate into Foxp3+ T cells [ 43 ], which might then suppress immune reaction and lead to worse survival.…”