Integration of chemokine signaling with non-coding RNAs in tumor microenvironment and heterogeneity in different cancers

Chemokines are small secreted proteins that regulate the immune system by signaling through chemokine receptors to induce immune cell migration, motility, and infiltration into the tissue. Altered chemokine/receptor expression is associated with numerous inflammatory diseases, and more recently in non-immune cell diseases like cancer. Emerging new studies demonstrate that chemokines can directly modulate the tumor microenvironment (TME) to assist tumorigenesis by regulating proinflammatory signaling, immune cell infiltration,and metastasis. However, the diversity and complexity in the regulation of chemokine expression and how chemokine receptor signaling influences TME needs comprehensive understanding. One mechanistic pathway that has shown promising early results in targeting tumor progression is the non-coding RNAs (ncRNAs). These are widely expressed and designated as prime gene regulatory factors in tumors and the immune system. Notably, ncRNAs have been implicated in regulating chromatin stability, translation of cytoplasmic mRNAs, and the functional regulation of membrane-less nuclear bodies, which are significant pathways implicated in tumorigenesis. Tissue-specific patterns of expression of ncRNAs have suggested their role as potential cancer biomarkers, providing a suitable rationale for targeting them clinically. In this review, we discuss the recent findings which demonstrate the role of differential expression of chemokines and ncRNA in modulating TME during tumor progression. We also discuss the communication between tumor and immune effector cells via chemokine/ncRNAs and identify their potential as novel therapeutic targets.