Immunomodulatory Gene-Splicing Dysregulation in Tumorigenesis: Unmasking the Complexity

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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.

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Toll-Like Receptor Signaling Pathways

Takumi Kawasaki, Taro Kawai (2014)

Toll-like receptors (TLRs) play crucial roles in the innate immune system by recognizing pathogen-associated molecular patterns derived from various microbes. TLRs signal through the recruitment of specific adaptor molecules, leading to activation of the transcription factors NF-κB and IRFs, which dictate the outcome of innate immune responses. During the past decade, the precise mechanisms underlying TLR signaling have been clarified by various approaches involving genetic, biochemical, structural, cell biological, and bioinformatics studies. TLR signaling appears to be divergent and to play important roles in many aspects of the innate immune responses to given pathogens. In this review, we describe recent progress in our understanding of TLR signaling regulation and its contributions to host defense.

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CTLA-4 and PD-1 Pathways

Elizabeth I Buchbinder, Anupam Desai (2016)

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PD-1/PD-L1 pathway: current researches in cancer.

Yanyan Han, Dandan Liu, Lianhong Li (2020)

Cancer immunotherapy has been accompanied by promising results over the past few years. Programmed Cell Death Protein 1 (PD-1) plays a vital role in inhibiting immune responses and promoting self-tolerance through modulating the activity of T-cells, activating apoptosis of antigen-specific T cells and inhibiting apoptosis of regulatory T cells. Programmed Cell Death Ligand 1 (PD-L1) is a trans-membrane protein that is considered to be a co-inhibitory factor of the immune response, it can combine with PD-1 to reduce the proliferation of PD-1 positive cells, inhibit their cytokine secretion and induce apoptosis. PD-L1 also plays an important role in various malignancies where it can attenuate the host immune response to tumor cells. Based on these perspectives, PD-1/PD-L1 axis is responsible for cancer immune escape and makes a huge effect on cancer therapy. This review is aimed to summarize the role of PD-1 and PD-L1 in cancer, looking forward to improve the therapy of cancer.