In:
Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 38, No. 15_suppl ( 2020-05-20), p. e21551-e21551
Abstract:
e21551 Background: Molecular characterization studies revealed recurrent KEAP1/ NFE2L2 alterations in non-small cell lung cancer (NSCLC). Previous studies have confirmed that KEAP1/NFE2L2 mutations are a poor prognostic factor for chemotherapy in patients with NSCLC. Nevertheless, it is unclear whether KEAP1/NFE2L2 mutations (MUT) of liquid biopsy can predict the efficacy of immunotherapy in NSCLC. Methods: Two independent cohorts (the OAK and POPLAR study cohort) with data from approximately 853 patients with advanced NSCLC were used to analyze the prognostic effect of KEAP1/NFE2L2 on immunotherapy. In addition, based on a deconvolution algorithm (known as CIBERSORT), we comprehensively analyzed the tumor-infiltrating immune cells present in NSCLC. The fraction of 22 immune cells subpopulations was evaluated to determine the associations between each cell type and KEAP1/NFE2L2 mutation status utilizing data from 1268 patients by lung adenocarcinoma (LUAD) and squamous cell lung carcinoma (LUSC) in TCGA pan-cancer cohort. Results: The OAK and POPLAR study cohort of NSCLC patients showed that KEAP1/NFE2L2 MUT was associated with poorer overall survival (OS), and progression-free survival (PFS) (OS: HR = 1.7, P 〈 0.001; PFS:HR = 1.4, P 〈 0.001) on immunotherapy, even after EGFR and ALK mutations were excluded, significant difference can also be gained (OS:HR = 1.8, P 〈 0.001; PFS:HR = 1.5, P 〈 0.001). Then, the NSCLC patients were subdivided into LUAD and LUSC, the OS and PFS of patients with KEAP1/NFE2L2 MUT is lower than wild-type (WT) (OS:HR = 1.8, P 〈 0.001; PFS:HR = 1.4, P = 0.0014) in LUAD, significant differences were obtained even when EGFR and ALK mutations were excluded (OS:HR = 1.9, P 〈 0.001;PFS:HR = 1.6, P 〈 0.001). In LUSC, patients with KEAP1/NFE2L2 MUT have lower OS (HR = 1.4, P = 0.0473),and there was no difference on PFS (HR = 1.2, P = 0.1588) between KEAP1/NFE2L2 MUT and WT, when EGFR and ALK mutations were excluded, the survival results did not change significantly. In addition, KEAP1/NFE2L2 MUT was positively correlated with infiltrating levels of plasma cells, T cells CD4 memory activated, T cells follicular helper, and Macrophages M1, but negatively correlated with infiltrating levels of T cells CD4 memory resting, monocytes, Dendritic cells activated, Mast cells resting, and Neutrophils in NSCLC. The immunoinfiltration of LUAD was significantly different from that of LUSC. Conclusions: These findings suggest that KEAP1/NFE2L2 can be used as a poorer biomarker for determining prognosis on immunotherapy and immune infiltration in NSCLC.
Type of Medium:
Online Resource
ISSN:
0732-183X
,
1527-7755
DOI:
10.1200/JCO.2020.38.15_suppl.e21551
Language:
English
Publisher:
American Society of Clinical Oncology (ASCO)
Publication Date:
2020
detail.hit.zdb_id:
2005181-5
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