Open Access<p>Primary Resistance to Immune Checkpoint Blockade in an <em>STK11/TP53/KRAS</em>-Mutant Lung Adenocarcinoma with High PD-L1 Expression</p>
Author(s) -
Won Gun Kwack,
So Youn Shin,
Seung Hyeun Lee
Publication year - 2020
Publication title -
oncotargets and therapy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.054
H-Index - 60
ISSN - 1178-6930
DOI - 10.2147/ott.s272013
Subject(s) - kras , blockade , stk11 , immune checkpoint , cancer research , mutant , adenocarcinoma , medicine , chemistry , mutation , cancer , gene , biochemistry , receptor
Several studies have shown that STK11 and TP53 mutations have different effects on the susceptibility to immune checkpoint blockade in KRAS -mutant non-small cell lung cancer (NSCLC). However, the impact of STK11/TP53 co-mutations on treatment outcomes in the same clinical setting has never been reported. We recently encountered a case of a 70-year-old man who was diagnosed with advanced lung adenocarcinoma with high-programmed death-ligand 1 (PD-L1) expression. He received pembrolizumab monotherapy as a frontline treatment; however, the tumor did not respond to this therapy and showed deleterious outcome. Next-generation sequencing revealed that the tumor harbored a rare STK11/TP53/KRAS triple mutation. Our case suggests that these compound mutations may constitute a distinct, aggressive subset that is resistant to immunotherapy even when the tumor strongly expresses PD-L1. In addition, this report highlights the importance of using molecular profiling to detect co-mutations that can be associated with primary resistance or disease progression to improve survival even in the immunotherapy setting.