The role of CD28 in the prognosis of young lung adenocarcinoma patients

Abstract

Background The prognosis of lung cancer was found to be associated with a series of biomarkers related to the tumor immune microenvironment (TIME), which can modulate the biological behaviors and consequent outcomes of lung cancer. Therefore, establishing a prognostic model based on the TIME for lung cancer patients, especially young patients with lung adenocarcinoma (LUAD), is urgently needed. Methods In all, 809 lung cancer patients from the TCGA database and 71 young patients with LUAD in our center were involved in this study. Univariate and multivariate analysis based on clinical characteristics and TIME-related expression patterns (as evaluated by IHC) were performed to estimate prognosis and were verified by prognostic nomograms. Results Both LUAD and lung cancer patients with high CD28 expression had shorter disease-free survival (DFS) (P = 0.0011; P = 0.0001) but longer overall survival (OS) (P = 0.0001; P = 0.0282). TIME-related molecules combined with clinical information and genomic signatures could predict the prognosis of young patients with LUAD with robust efficiency and could be verified by the established nomogram based on the Cox regression model. In addition, CD28 expression was correlated with an abundance of lymphocytes and could modulate the TIME. Higher CD28 levels were observed in primary tumors than in metastatic tissues. Conclusion TIME-related molecules were identified as compelling biomarkers for predicting the prognosis of lung cancer, especially in a cohort of young patients. Furthermore, CD28, which is associated with poor DFS but long OS, might participate in the modulation of the TIME and has a different role in the prognosis of young patients with LUAD.

The Potential Predictive Biomarkers for Advanced Hepatocellular Carcinoma Treated With Anti-Angiogenic Drugs in Combination With PD-1 Antibody

“…This finding indicates that the CD28 pathway may reverse the immuno-suppressive state. Furthermore, in lung adenocarcinoma, patients with high CD28 expression have lower disease-free survival (DFS) ( 20 ). The high expression of CD28 in the SD in our study was consistent with the above-mentioned conclusion, indicating that the high baseline status of CD28 might exhaust the ability of the co-stimulatory pathway to reverse immunosuppression, which led to the occurrence and development of tumors.…”

Expression of CD28 in Hepatocellular Carcinoma and Its Prognostic Value

“…Similarly, clinical significance analysis of CD28 in leukemia (ATL) revealed that patients with genetic abnormalities related to CD28 exhibited a worse prognosis than those without, indicating the beneficial effects of CD28 expression on the survival time of ATL patients (25). Controversially, the high expression of CD28 in lung cancer patients was associated with worse disease-free survival but a better overall survival (26). Thus, we speculated that CD28 might play a different role in the prognosis of different can-Besides, our results showed that the CD28 expression was significantly correlated with the number of CD4+ and CD8+ T-cells.…”

Telomere Shortening and Its Association with Cell Dysfunction in Lung Diseases

“…It is likely that these cytotoxic cells are involved in the high morbidity of fibrotic interstitial lung diseases in patients with telomere dysfunction after a lung transplant. It seems that the status of CD28+ T cells behaves as a double-edged sword: an increase in CD28+ cells is tumorigenic in the early stage but related to more prolonged survival, and loss of CD28 is related to metastasis [ 111 , 112 ]. In contrast, a consequence of accumulating CD8+/CD28− T cells is that they can lose their function, have reduced expression of effector molecules (granzyme B and perforin), and reduced cytotoxic T-lymphocyte (CTL) activity [ 113 ].…”