AUTHOR=Chen Xiao-Juan , Ren Ai-Qun , Zheng Liang , Zheng En-Dian 

TITLE=Predictive Value of KDM5C Alterations for Immune Checkpoint Inhibitors Treatment Outcomes in Patients With Cancer

JOURNAL=Frontiers in Immunology

VOLUME=12

YEAR=2021

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2021.664847

DOI=10.3389/fimmu.2021.664847

ISSN=1664-3224

ABSTRACT=<p>Lysine (K)-specific demethylase 5C (<italic>KDM5C</italic>) plays a significant role in the tumor cell proliferation, invasion, drug resistance and the regulation of tumor-related gene expression. Here, we aimed to investigate its predictive value in patients with cancers received immune checkpoint inhibitors (ICIs). We explored the predictive value of <italic>KDM5C</italic> alterations and the association between <italic>KDM5C</italic> alteration and immune landscape by using published cohort with clinical outcome and sequenced data from online database. The frequency of <italic>KDM5C</italic> alterations was 2.1% across 48045 tumor samples with different cancers from 185 studies. <italic>KDM5C</italic> alterations were correlated with markedly inferior overall survival (OS, 53 vs. 102 months, <italic>P</italic>&lt;0.0001) than those without. However, in ICI-treated group, patients with <italic>KDM5C</italic> alterations had a substantially prolonged OS than the wild-type group (not reached vs. 18 months, <italic>P</italic>=0.0041). The predictive value of <italic>KDM5C</italic> alterations for ICI treatment outcome was not observed in patients with microsatellite-stable tumors (<italic>P</italic>=0.2875). Intriguingly, patients with non-small-cell lung cancer and <italic>KDM5C</italic> alterations receiving ICI had the better progression-free survival than wild type group (13.2 vs. 3.2 months, <italic>P</italic>=0.0762). Mechanistically, <italic>KDM5C</italic> altered tumors had dramatically higher TMB level and was associated with significantly higher level of CD8+ T cell infiltration and T effector signature. In conclusion, <italic>KDM5C</italic> alterations was correlated with enhanced tumor immunogenicity and inflamed anti-tumor immunity, thus resulting in better treatment outcome in cancer patients receiving ICIs.</p>