Background: Tumor microenvironment (TME) cells play important roles in tumor
progression. Accumulating evidence show that they can be exploited to predict the clinical
outcomes and therapeutic responses of the tumor. However, the role of immune genes of TME in
small cell lung cancer (SCLC) is currently unknown.
Objective: To determine the role of immune genes in SCLC.
Methods: We downloaded the expression profile and clinical follow-up data of SCLC patients
from Gene Expression Omnibus (GEO), and TME infiltration profile data of 158 patients using
CIBERSORT. The correlation between TME phenotypes, genomic features, and
clinicopathological features of SCLC was examined. A gene signature was constructed based on
TME genes to further evaluate the relationship between molecular subtypes of SCLC with the
prognosis and clinical features.
Results: We identified a group of genes that are highly associated with TME. Several immune cells
in TME cells were significantly correlated with SCLC prognosis (p<0.0001). These immune cells
displayed diverse immune patterns. Three molecular subtypes of SCLC (TMEC1-3) were
identified on the basis of enrichment of immune cell components, and these subtypes showed
dissimilar prognosis profiles (p=0.03). The subtype with the best prognosis, TMEC3, was enriched
with immune activation factors such as oncogene M0, oncogene M2, T cells follicular helper, and
T cells CD8 (p<0.001). The TMEC1 subtype with the worst prognosis was enriched with T cells
CD4 naive, B cells memory and Dendritic cells activated cells (p<0.001). Further analysis showed
that the TME was significantly enriched with immune checkpoint genes, immune genes, and
immune pathway genes (p<0.01). From the gene expression data, we identified four TME-related
genes, GZMB, HAVCR2, PRF1 and TBX2, which were significantly associated with poor
prognosis in both the training set and the validation set (p<0.05). These genes may serve as
markers for monitoring tumor responses to immune checkpoint inhibitors.
Conclusion: This study shows that TME features may serve as markers for evaluating the response
of SCLC cells to immunotherapy.