Roles and potential applications of non-coding RNAs in cancer treatment with immune checkpoint inhibitors and immunomodulatory therapies

Abstract

Non-coding RNAs (ncRNAs) have emerged as key regulators of cancer–immune crosstalk, especially in an era when immune checkpoint inhibitors and other immunomodulatory therapies are reshaping the cancer treatment landscape. Accumulating evidence continues to indicate that ncRNAs, including microRNAs, long non-coding RNAs and circular RNAs, critically connect oncological signaling with immune interactions, thereby influencing clinical outcomes. In this review, we summarize how ncRNAs modulate key immune checkpoint axes, particularly programmed cell death protein 1 (PD-1)/programmed cell death ligand 1 (PD-L1) and cytotoxic T-lymphocyte antigen 4 (CTLA-4). We also discuss ncRNA networks that are actively involved in modern cancer immunotherapies, such as T cell–based therapies, macrophage and dendritic cell engineering, cytokine therapies, cancer vaccines and oncolytic viruses. Building on these mechanistic insights, we outline the potential of ncRNAs as biomarkers for predicting response and prognosis, as future therapeutic targets to improve and enhance immunotherapy combinations, along with key barriers in the field and emerging solutions. Altogether, the evidence not only highlights ncRNAs as rising stars in precision immuno-oncology, but also motivates future opportunities to incorporate ncRNAs into clinical consideration.

Keywords

Non-coding RNA / cancer / therapy / immunotherapy / immune checkpoint inhibitors

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