Abstract:
The molecular understanding of carcinogenesis and tumor progression rests in intra and
inter-tumoral heterogeneity. Solid tumors confined with vast diversity of genetic
abnormalities, epigenetic modifications, and environmental cues that differ at each
stage from tumor initiation, progression, and metastasis. Complexity within tumors
studied by conventional molecular techniques fails to identify different subclasses in
stromal and immune cells in individuals and that affects immunotherapies. Here we focus
on diversity of stromal cell population and immune inhabitants, whose subtypes create the
complexity of tumor microenvironment (TME), leading primary tumors towards advancedstage cancers. Recent advances in single-cell sequencing (epitope profiling) approach
circumscribes phenotypic markers, molecular pathways, and evolutionary trajectories of
an individual cell. We discussed the current knowledge of stromal and immune cell
subclasses at different stages of cancer development with the regulatory role of noncoding RNAs. Finally, we reported the current therapeutic options in immunotherapies,
advances in therapies targeting heterogeneity, and possible outcomes.