Abstract 1250P
Background
KRAS is the most common oncogenic driver in NSCLC. Researchers previously reported that only KRAS mutation and KRAS co-mutated with STK11 define distinct subgroups of NSCLC, which response differently to immune checkpoint inhibitors (ICI). Herein, by means of evaluating the tumor immune microenvironment (TME) and some biomarkers, to explore the mechanism of different efficacy of ICI showed in these subgroup of Chinese NSCLC patients.
Methods
The formalin-fixed paraffin-embedded specimens of cancer patients who have underwent next-generation sequencing (NGS) from May 2017 to May 2020, were included in this study. NGS was performed to detect gene mutation, and tumor mutational burden (TMB) measured by a 733 gene panel. PD-L1 expression detected by using Dako PD-L1 IHC 22C3 pharmDx, TIME was detected by multiple IHC (mIHC).
Results
3323 Chinese patients with NSCLC were admitted to NGS and TME detection, among them, 1002 samples were available for TMB analysis, and 796 were available for PD-L1 expression analysis, and 19 were available for TME evaluation. Three subgroups were distinguished as group of only KRAS mutation, only STK11, and co-mutation of KRAS and STK11. The median TMB level was slightly lower in co-mutation group than others, while no significant difference was found in the TMB level of three subgroups. Results of IHC showed PD-L1 expression level was significantly higher in KRAS mutation group than in SKT11 mutation or co-mutation groups (p<0.001). What’s more, mIHC revealed that, both in STK11 group and co-mutation group, the number of positive immune cell infiltrated in tumor was lower than in KRAS mutation group, such as CD8+T cells, M1 TAM, CD56dim NK cells.
Conclusions
The different response to ICI in patients with KRAS mutation, co-mutation with STK11 can be explained by the difference in TIME, which including immune cells infiltrated, PD-L1 expression.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
H. Zhang, X. Shen, D. Huang: Financial Interests, Institutional, Full or part-time Employment: 3D Medicine Inc. All other authors have declared no conflicts of interest.