A TP53 Related Immune Prognostic Model for the Prediction of Clinical Outcomes and Therapeutic Responses in Lung Adenocarcinoma

Abstract

TP53 is the most frequently mutated gene in lung adenocarcinoma (LUAD). The tumor immune microenvironment (TIM) is considered a vital factor that influences tumor progression and survival rate. The influence of TP53 mutation on TIM in LUAD has not been fully studied. Here we systematically investigated the relationship and potential mechanisms between TP53 mutation status and immune response in LUAD. We constructed an immune prognostic model (IPM) using immune associated genes, which were expressed differentially between the TP53 mutant and wild type LUAD patients. We discovered that TP53 mutations were significantly associated with 5 immune related biological processes. Thirty-six immune genes were expressed differentially between TP53 mutant and wild type LUAD patients. An IPM was constructed using 3 immune genes to differentiate the prognostic survival in LUAD. The high-risk LUAD group displayed significantly higher proportions of dendritic cell resting, T cell CD4 memory resting and mast cell resting, and significantly low proportions of dendritic cell activated, T cell CD4 memory activated, and mast cell activated. Moreover, IPM was found to be an independent clinical feature and can be used to predict immunotherapy responses. In summary, we constructed and validated an IPM using 3 immune related genes, which provides a better understanding of the mechanism from an immunological perspectives.

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“…It has been shown that a high density of cytotoxic immune cells, such as CD8 T cells and NK cells, in the tumor microenvironment is correlated with improved outcome in patients with EC 7,8,24 . On the other hand, the presence of resting memory CD4T cells indicates impaired immune response, and is associated with unfavorable prognosis in cases of melanoma, urothelial cancer, thyroid carcinoma, gastric cancer and lung adenocarcinoma 25–28 . While DCs are thought to present tumor‐associated antigens to naive T cells and contribute to an anti‐tumor role, our findings indicated that high levels of activated DCs within the tumor were inversely correlated with densities of CD8 T cells, and predicted worse outcome for patients with EC.…”

“… 7 , 8 , 24 On the other hand, the presence of resting memory CD4T cells indicates impaired immune response, and is associated with unfavorable prognosis in cases of melanoma, urothelial cancer, thyroid carcinoma, gastric cancer and lung adenocarcinoma. 25 , 26 , 27 , 28 While DCs are thought to present tumor‐associated antigens to naive T cells and contribute to an anti‐tumor role, our findings indicated that high levels of activated DCs within the tumor were inversely correlated with densities of CD8 T cells, and predicted worse outcome for patients with EC. Jensen et al 29 reported that higher levels of intratumoral plasmacytoid dendritic cells (CD123+) were ultimately correlated with worse survival, indicating that DCs play a dual role in tumor progression.…”