Maebele, Lorraine TshegofatsoMulaudzi, Thanyani VictorYasasve, MadhavanDlamini, ZodwaDamane, Botle Precious2024-08-302024-08-302023-08-10Maebele, L.T.; Mulaudzi, T.V.; Yasasve, M.; Dlamini, Z.; Damane, B.P. Immunomodulatory Gene-Splicing Dysregulation in Tumorigenesis: Unmasking the Complexity. Molecules 2023, 28, 5984. https://DOI.org/10.3390/molecules28165984.1420-3049 (online)10.3390/molecules28165984http://hdl.handle.net/2263/97953Cancer is a global health concern with rising incidence, morbidity, and mortality. The interaction between the tumor and immune cells within the tumor microenvironment is facilitated by signaling pathways driven by immunomodulatory proteins. Alternative splicing regulates the production of multiple immunomodulatory proteins with diverse functionality from a single mRNA transcript. Splicing factors are pivotal in modulating alternative splicing processes but are also subject to regulation. The dysregulation of alternative splicing may result from splicing factor (SF) abnormal expression levels and mutations in the cis and trans-acting elements and small nuclear RNA (snRNA) molecules. Aberrant splicing may generate abnormal mRNA transcripts encoding isoforms with altered functions that contribute to tumorigenesis or cancer progression. This review uncovers the complexity of immunomodulatory genes splicing dysregulation in oncogenesis. Identifying specific immunomodulatory splicing isoforms that contribute to cancer could be utilized to improve current immunotherapeutic drugs or develop novel therapeutic interventions for cancer.en© 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license.Alternative splicingIsoformsImmune checkpointsImmunomodulatory proteinsSplicing factorsSDG-03: Good health and well-beingSmall nuclear RNA (snRNA)Ribonucleic acid (RNA)Article