Remodeling of Stromal Cells and Immune Landscape in Microenvironment During Tumor Progression

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 advanced-stage 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 non-coding RNAs. Finally, we reported the current therapeutic options in immunotherapies, advances in therapies targeting heterogeneity, and possible outcomes.

Autophagy Drives Galectin-1 Secretion From Tumor-Associated Macrophages Facilitating Hepatocellular Carcinoma Progression

“…Of note, emerging evidence has defined the crucial role of the tumor microenvironment (TME) in the development and progression of HCC ( Santhakumar et al, 2020 ). The cellular and non-cellular components of the tumor niche supporting the tumor growth and metastasis comprise TME, where dynamic interactions between cancer cells and immune cells significantly impact tumor growth and therapy efficacy ( Wang et al, 2017 ; Arora and Pal, 2021 ). A significant subpopulation of immune cells in TME is that of tumor-associated macrophages (TAMs), whose function is evidently to promote the tumor progression, even though it was first thought to be a host immune response against the growing tumors.…”

Overexpression of prothymosin-α in glioma is associated with tumor aggressiveness and poor prognosis

“…PTMA has been shown to regulate cell proliferation and induction of type I interferon immunomodulatory activity in human macrophages [ 63 , 64 ]. PTMA has also been reported to be expressed by a subclass of neutrophils N2, present in lung tissue with unknown functions [ 65 ].…”

Altered BMP2/4 Signaling in Stem Cells and Their Niche: Different Cancers but Similar Mechanisms, the Example of Myeloid Leukemia and Breast Cancer

“…Main hypotheses suggest that CSC resistance reflect the preservation of intrinsic protective mechanisms unique to the SC compartment or the re-emergence of these properties in cancer cells ( O'Brien-Ball and Biddle, 2017 ). In addition, CSCs and their niche are engaged in a crosstalk regulating several SC-signaling pathways, as well as niche features ( Arora and Pal, 2021 ). BMP2 and BMP4, produced within the SC microenvironment, are master regulators of the functions of tissue-specific SC and their surrounding MSC and emerge as key players of SC transformation.…”