BACKGROUND@#
Lung cancer is a malignant with high
incidence and
mortality and
adenocarcinoma is among the most popular subtypes.
Epidermal growth factor receptor (EGFR)
mutation is one of the most important driver
mutations for
lung adenocarcinoma and EGFR-
tyrosine kinase inhibitor (TKI)
will benefit those
patients with sensitive EGFR
mutations. Recently, immune checkpoint inhibitor (ICI)
therapy, provide a new breakthrough
treatment for
lung cancer patients. Whereas
immunotherapy as an emerging
treatment does not benefit
patients with EGFR
mutations, for which mechanistic studies are poorly defined and focused on the link of EGFR
mutations and
programmed cell death-
ligand 1 (PD-L1) expression, we speculate that the different immune microenvironment associated with the two classes of
patients.@*
METHODS@#
Lung adenocarcinoma datasets were collected from the
Cancer Genome Atlas (TCGA) database, and clinical information and
gene expression profiles were downloaded. The immune related
lymphocyte infiltration in TCGA database were generated through timer 2.0 GSEA was used to analyze the difference of pathway expression between EGFR mutant
patients and wild type
patients.@*RESULTS@#EGFR
mutation was more frequently among
women and never
smokers. Immunoinfiltration
analysis showed that
patients with EGFR
mutation tends to have more
tumor associated fibroblasts,
common myeloid progenitor cells, hematopoietic stem cells, effector CD4⁺
T cells and
natural killer T cells infiltration, and less
memory B cells, naïve B
cells, plasma B
cells, plasmacytoid dendritic cells,
memory CD4⁺
T cells, CD4⁺
helper T cells 2, naive CD8⁺
T cells, CD8⁺
T cells and central
memory CD8⁺
T cells infiltration. Moreover,
patients with more infiltration of CD8⁺
T cells,
natural killer T cells,
memory B cells and
hematopoietic stem cells, tends have better
prognosis (Log-rank test, P=0.017, 0.0093, 0.018, 0.016). However, the
patients with more CD4⁺ T th2 infiltration in the
tumor tends to have worse
prognosis (Log-rank test, P=0.016). Furthermore, the results of
gene set enrichment
analysis showed that compared with the
lung adenocarcinoma patients with EGFR wild type, the three pathways positive
regulation of natural killer (NK)
cell-mediated
immune response to
tumor cells, NK cell activation involved in
immune response, and
NK cell-mediated
immune response to
tumor cells related to
natural killer cells in
patients with EGFR
mutation were down regulated, while the pathway the positive
regulation of
cytokine secretion involved in
immune response was up-regulated in EGFR
mutation patients.@*CONCLUSIONS@#The tumour microenvironment of
patients with EGFR
mutations lacks potent tumour
killing effector
cells and appears dysfunctional with effector
cells. This may be a potential reason for the poor
efficacy of
immunotherapy in
patients with EGFR
mutations.