OBJECTIVES: The efficacy of anti- programmed cell death 1 (PD-1)/PD-1 ligand 
(PD-L1) immune checkpoint inhibitors remains controversial in patients with KRAS 
mutation. In addition, whether and how KRAS gene and its mutant subtypes might 
influence immunity has not been clarified yet. Here we examine some important 
biomarkers for the efficacy of immunotherapy in specific KRAS subtypes.
MATERIALS AND METHODS: We conducted a bioinformatics analysis on somatic 
mutations data, transcriptome sequencing data and proteomic data from The Cancer 
Genome Atlas (TCGA) database. CIBERSORT was used to provide an estimation of the 
abundances of immune cells using gene expression data.
RESULTS: From a cohort of 567 patients with lung adenocarcinoma (LUAD) based on 
TCGA, the overall mutation rate of KRAS was 26.29 %, including KRAS/TP53 
co-mutation rate of 9.7 %. We observed increased Tumor mutation burden (TMB) in 
KRAS mutant group compared with wild type, while no difference in PD-L1 
expression and immune cell infiltration. More importantly, TP53 and KRAS/TP53 
co-mutation group not only significantly increased tumor mutation burden, but 
also had higher PD-L1 protein level and immune cell infiltration. We further 
focused on influence of KRAS mutant subtype on immune biomarker. The most 
prevalent mutant subtype of KRAS in lung adenocarcinoma was G12C(9.88 %,56/567), 
followed by G12 V(5.82 %,33/567), G12D(3.00 %,17/567), G12A(3.00 %,17/567), 
respectively. Among them, G12D mutation appeared to be a special mutant subtype 
with an obviously lower TMB. This low mutation load was more significant when 
co-mutation with TP53. Besides, our results also revealed significantly 
decreased expressions of PD-L1 protein level and immune cell infiltration 
(activated CD4 memory T cell, helper T cell, M1 macrophage and NK cell) in KRAS 
G12D/TP53 mutant group.
CONCLUSION: KRAS G12D/TP53 co-mutation drives immune suppression and might be a 
negative predictive biomarker for anti-PD-1/PD-L1 immune checkpoint inhibitors 
in patients with lung adenocarcinoma.