Abstract:
Cancer 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.
