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Background: Ephrin type-A receptors (EPHA) are members of family of receptor tyrosine kinases and are related to tumor immunogenicity and immune microenvironment, however, the association between mutation ( ) and efficacy of immune checkpoint inhibitors (ICIs) has not been investigated in non-small cell lung cancer (NSCLC).
Methods: Multiple cohorts were used to assess the immunotherapeutic predictive performance of , including one discovery cohort (n=79) and two public validation cohort (cohort 1: NSCLC, n=165; cohort 2: pan-cancer, n=1662). The Cancer Genome Atlas cohort was used for prognostic analysis and mechanism exploration.
Results: In the discovery cohort, patients with had superior disease control rate (72.2% vs 36.1%, p=0.01) and progression-free survival (PFS) (HR 0.38; 95% CI 0.21 to 0.68; p<0.001) compared with those with wide-type ( ) in NSCLC. The association between and immunotherapy outcomes in NSCLC was consistently observed in the validation cohorts by multivariable models (cohort 1, PFS HR 0.59; 95% CI 0.37 to 0.96; p=0.03; cohort 2, overall survival (OS) HR 0.63; 95% CI 0.41 to 0.98; p=0.04). Further pooled estimates of the discovery and validation cohorts showed that patients with exhibited a significantly longer PFS and OS in lung adenocarcinoma (LUAD) while not squamous cell lung cancer (LUSC). Consistently, mechanism analysis revealed that patients with was associated with increased T cell signatures and downregulated signaling compared with patients with in LUAD while not LUSC.
Conclusions: Our results demonstrated that is an independent classifier that could stratify patients with LUAD for ICIs therapy. Further prospective studies are warranted.
Trial Registration Number: NCC2016JZ-03, NCC2018-092.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7733211 | PMC |
| http://dx.doi.org/10.1136/jitc-2020-001315 | DOI Listing |
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