Dataset Information

The Prognosis and Immune Checkpoint Blockade Efficacy Prediction of Tumor-Infiltrating Immune Cells in Lung Cancer.

ABSTRACT:

Backgrounds

The high morbidity and mortality of lung cancer are serious public health problems. The prognosis of lung cancer and whether to apply immune checkpoint blockade (ICB) are currently urgent problems to be solved.

Methods

Using R software, we performed Kaplan-Meier (K-M) analysis, Cox regression analysis, functional enrichment analysis, Spearman correlation analysis, and the single-sample gene set enrichment analysis.

Results

On the Tumor IMmune Estimation Resource (TIMER2.0) website, we calculated the abundance of tumor-infiltrating immune cells (TIICs) of lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) patients. B cell and myeloid dendritic cell (DC1) were independent prognostic factors for LUAD and LUSC patients, respectively. Enrichment analysis confirmed that genes highly related to B cell or DC1 were closely related to the immune activation of lung cancer patients. In terms of adaptive immune resistance markers, CD8A, CD8B, immunomodulators (immunostimulants, major histocompatibility complex, receptors, and chemokines), immune-related pathways, tumor microenvironment score, and TIICs, high B cell/DC1 infiltration tissue was inflamed and immune-activated and might benefit more from the ICB. Genes most related to B cell [CD19, toll-like receptor 10 (TLR10), and Fc receptor-like A (FCRLA)] and DC1 (ITGB2, LAPTM5, and SLC7A7) partially clarified the roles of B cell/DC1 in predicting ICB efficacy. Among the 186 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, there were three and four KEGG pathways, which partially explained the molecular mechanisms by which B cell and DC1 simultaneously predicted the prognosis and efficacy of immunotherapy, respectively. Among five immune subtypes, the abundance of B cell/DC1 and expression of six hub genes were higher in immune C2, C3, and C6.

Conclusion

B cell and DC1 could predict the prognosis and ICB efficacy of LUAD and LUSC patients, respectively. The six hub genes and seven KEGG pathways might be novel immunotherapy targets. Immune C2, C3, and C6 subtypes of lung cancer patients might benefit more from ICB therapy.

SUBMITTER: Liu X

PROVIDER: S-EPMC8370893 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Background To depict the immune infiltration characteristics of tumor cells in patients with lung adenocarcinoma (LUAD) and evaluate the predictive value and significance of tumor immune cells on the prognosis of LUAD patients. Methods The clinical characteristics and transcriptome of LUAD patients were obtained from The Cancer Genome Atlas (TCGA), and the immune cell abundance in LUAD tissue was evaluated using the CIBERSORT algorithm. We created a simplified immune cell-based Cox regression model according to the survival status of patients and clarified the correlation between the survival status of patients and seven types of immune cells. An immune cell-based risk prediction model was created by Cox proportional hazards regression. Subsequently, the gene expression profile of LUAD patients was obtained from the Gene Expression Omnibus (GEO) database to validate the tumor immune infiltration and patient prognosis prediction model attained using the CIBERSORT algorithm. Results The abundance of 22 tumor-infiltrating immune cells in these patients was detected using the CIBERSORT algorithm. According to Pearson correlation analysis, the immune cells appeared to be closely related to each other. The immune cell composition was remarkably different between the LUAD tumor tissue and paracancerous tissue. The simplified COX model showed that seven kinds of immune cells have predictive value for the prognosis and survival status of LUAD. The receiver operating characteristic curve (ROC) curve confirmed that the prediction model performed well for 1-, 3-, and 5-year survival status. The calibration curve suggested that the prediction model was consistent with the clinical results. Correlation analysis revealed that the clinical features were significantly related to immune cell infiltration. A total of 246 LUAD specimens were from the GEO database, and the risk score model suggested that high risk scores were indicative of a poor prognosis. Finally, enzyme-linked immunosorbent assay (ELISA) revealed that the expressions of tumor necrosis factor-α (TNF-α), interleukin 8 (IL-8), IL-6, and interferon-γ (IFN-γ) in tumor tissues were remarkably higher compared with those in adjacent tissues. Conclusions There is a close correlation between the tumor-infiltrating immune cells and the prognosis and clinical characteristics of LUAD patients. The risk score model based on TCGA and GEO designed in this study can be applied in clinical practice.

Project description:ObjectiveIncreasing evidence has indicated an association between immune cells infiltration in LSCC and clinical outcome. The aim of this research was tantamount to comprehensively investigate the effect of 22 tumor infiltrating immune cells (TIICs) on the prognosis of LSCC patients.MethodsIn our research, the CIBERSORT algorithm was utilized to calculate the proportion of 22 TIICs in 502 cases from the TCGA cohort. Cases with a CIBERSORT P-value of <0.05 were kept for further study. Using the CIBERSORT algorithm, we first investigated the difference of immune infiltration between normal tissue and LSCC in 22 subpopulations of immune cells. Kaplan-Meier analysis was used to analyze the effect of 22 TIICs on the prognosis of LSCC. An immune risk score model was constructed based on TIICs correlated with LSCC-related recurrence. Multivariate cox regression analysis was used to investigate whether the immune risk score was an independent factor for prognosis prediction of LSCC. Nomogram was under construction to comprehensively predict the survival rate of LSCC.ResultsThe results of the different analysis showed that except of memory B cells, naive CD4+T cells, T cells and activated NK cells, the remaining immune cells all had differential infiltration in normal tissues and LSCC (p < 0.05). Kaplan-Meier analysis revealed two immune cells statistically related to LSCC-related recurrence, including activated mast cells and follicular helper T cells. Immune risk score model was constructed based on three immune cells including resting memory CD4+T cells, activated mast cells and follicular helper T cells retained by forward stepwise regression analysis. The Kaplan-Meier curve indicated that patients in the high-risk group linked to poor outcome (P = 8.277e-03). ROC curve indicated that the immune risk score model was reliable in predicting recurrence risk (AUC = 0.614). Multivariate cox regression analysis showed that the immune risk score model was just an independent factor for prognosis prediction of LSCC (HR = 2.99, 95% CI [1.65-5.40]; P = 0.0002). The nomogram model combined immune risk score and clinicopathologic parameter score to predict 3-year survival in patients with LSCC.ConclusionsCollectively, tumor-infiltrating immune cells play a major role in the prognosis of LSCC.