The immune microenvironment in EGFR- and ERBB2-mutated lung adenocarcinoma

ESMO Open ◽  
2021 ◽  
Vol 6 (5) ◽  
pp. 100253
M. Kirchner ◽  
K. Kluck ◽  
R. Brandt ◽  
A.-L. Volckmar ◽  
R. Penzel ◽  
2020 ◽  
Vol 121 (5-6) ◽  
pp. 3208-3220 ◽  
Qian Song ◽  
Jun Shang ◽  
Chufan Zhang ◽  
Jianing Chen ◽  
Lanlin Zhang ◽  

2015 ◽  
Vol 33 (15_suppl) ◽  
pp. 11002-11002 ◽  
Ferdinandos Skoulidis ◽  
Warren Denning ◽  
Lixia Diao ◽  
Pan Tong ◽  
You Hong Fan ◽  

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e20625-e20625
Yuqiao Chen ◽  
Xinying Shi ◽  
Xue Song ◽  
Lingling Gao ◽  
Beibei Mao ◽  

e20625 Background: The resection of early stage NSCLC offers patients the best hope of a cure. However, the recurrence rate post-resection remains high. As the mechanisms involved in the process is still not clear due to the unavailability of accurate targets, our study was aimed to integrate the impact of different immune context present in lung adenocarcinoma (LUAD) microenvironment on patients’ prognosis. Methods: RNA targeted sequencing was performed on 24 primary tumor specimens from the resected local advanced LUADs . Transcripts of 395 immune related genes expressed in FFPE tumor samples were analyzed. The limma package was used to analyze the different expressed genes (DEGs) between patients with different prognosis. The gene set variance analysis (GSVA) analysis was performed to explore gene sets enrichment related to the prognosis (PFS, progression free survival) post-resection. Results: 23 DEGs were detected in primary tumor between the better (PFS > 18months, n = 12 ) and worse (PFS≤18months, n = 12 ) prognosis group. The combined prediction model containing MPO, IL-6, CXCR2, FCGR3B, ADGRE5 could identify the favorable prognosis of patients. GSVA and Log Rank test of survival data demonstrated that the antigen processing and lymphocyte activation pathway enrichment may associate with better prognosis (p = 0.01), whereas higher Neutrophils cell infiltration in primary tumor demonstrated a shorter PFS (p = 0.008). Conclusions: In LUAD, the immune related genes such as MPO, IL-6, CXCR2, FCGR3B, ADGRE5, can effectively profile the landscape of tumor immune microenvironment and predict the survival in early stage of lung adenocarcinoma. Accordingly immune pathways were correlated with prognosis of these patients. Our findings suggest that immune-related RNA expression pattern in locally advanced LUAD may provide a potential predictive marker for early recurrence after surgical resection.

2020 ◽  
Vol 204 (8) ◽  
pp. 2295-2307 ◽  
Amber M. Johnson ◽  
Bonnie L. Bullock ◽  
Alexander J. Neuwelt ◽  
Joanna M. Poczobutt ◽  
Rachael E. Kaspar ◽  

2020 ◽  
Vol 11 (24) ◽  
pp. 7101-7115
Jianguo Zhang ◽  
Jianzhong Zhang ◽  
Cheng Yuan ◽  
Yuan Luo ◽  
Yangyi Li ◽  

2021 ◽  
Zhenyu Zhao ◽  
Boxue He ◽  
Qidong Cai ◽  
Pengfei Zhang ◽  
Xiong Peng ◽  

Abstract Background: Lung adenocarcinoma (LUAD) accounts for a majority of cancer-related deaths worldwide annually. A recent study shows that immunotherapy is an effective method of LUAD treatment, and tumor mutation burden (TMB) was associated with the immune microenvironment and affected the immunotherapy. Exploration of the gene signature associated with tumor mutation burden and immune infiltrates in predicting prognosis in lung adenocarcinoma in this study, we explored the correlation of TMB with immune infiltration and prognosis in LUAD.Materials and Methods: In this study, we firstly got mutation data and LUAD RNA-Seq data of the LUAD from The Cancer Genome Atlas (TCGA), and according to the TMB we divided the patients into high/low-TMB levels groups. The gene ontology (GO) pathway enrichment analysis and KOBAS-Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways analysis were utilized to explore the molecular function of the differentially expressed genes (DEGs) between the two groups. The function enrichment analyses of DEGs were related to the immune pathways. Then, the ESTIMATE algorithm, CIBERSORT, and ssGSEA analysis were utilized to identify the relationship between TMB subgroups and immune infiltration. According to the results, Venn analysis was utilized to select the immune-related genes in DEGs. Univariate and Lasso Cox proportional hazards regression analyses were performed to construct the signature which positively associated with the immune infiltration and affected the survival. Finally, we verified the correlation between the signature and immune infiltration. Result: The exploration of the immune infiltration suggested that high-TMB subgroups positively associated with the high level of immune infiltration in LUAD patients. According to the TMB-related immune signature, the patients were divided into High/Low-risk groups, and the high-risk group was positively associated with poor prognostic. The results of the PCA analysis confirmed the validity of the signature. We also verified the effectiveness of the signature in GSE30219 and GSE72094 datasets. The ROC curves and C-index suggested the good clinical application of the TMB-related immune signature in LUAD prognosis. Another result suggested that the patients of the high-risk group were positively associated with higher TMB levels, PD-L1expression, and immune infiltration levels.Conclusion: In conclusion, our signature provides potential biomarkers for studying aspects of the TMB in LUAD such as TMB affected immune microenvironment and prognosis. This signature may provide some biomarkers which could improve the biomarkers of PD-L1 immunotherapy response and were inverted for the clinical application of the TMB in LUAD. LUAD male patients with higher TMB-levels and risk scores may benefit from immunotherapy. The high-risk patients along with higher PD-L1 expression of the signature may suitable for immunotherapy and improve their survival by detecting the TMB of LUAD.

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