Table 2 Aberrant RNA splicing and immune regulation.
From: The potential impact of RNA splicing abnormalities on immune regulation in endometrial cancer
Cell type | Aberrant RNA splicing event | Impact on immune regulation | Reference |
|---|---|---|---|
Tumor cells | Aberrant splicing of PD-L1 (scePD-L1) | Interferes with PD-1/PD-L1 signaling, aiding immune evasion | [102] |
| Â | DCLK1-isoform2 | Causes M1 macrophages to shift towards M2, impeding CD8+ T cell growth | [103] |
| Â | Aberrant splicing of CTLA-4 (sCTLA-4) | Blocks CD8+ T cell activation | [104] |
|  | HER2Δ6 | Lowers IFN expression, produces adenosine with immunosuppressive effects, and inhibits T cell and macrophage infiltration in tumors | [105] |
| Â | Activation of SRSFs and degradation of RBM39 | Generates novel antigens, enhancing immunotherapy responsiveness | |
| Â | JETs (Junctions of Exons to non-coding Transcripts) | Presents new splice variants as antigens, inducing antitumor immune response | [108] |
| Â | Intron retention mechanism | Generates dsRNA, triggering antiviral signaling pathways and improving immune surveillance | [109] |
Macrophages | MyD88 splice variants (MyD88L and MyD88S) | MyD88S limits immune activation by failing to bind NF-κB | [113] |
|  | Soluble TLR4 (sTLR4) | Suppresses NF-κB signaling and TNF-α generation | [119] |
|  | NLRP3 splice variants (full-length and NLRP3-Δ5) | NLRP3-Δ5 lacks LRR domain, preventing caspase-1 activation | [121] |
| Â | FKBP51 splice variant (FKBP51s) | Alters macrophage activity, promoting M2-type activation and inhibiting antigen presentation | [122] |
| Â | Acly splice variants (Acly L and Acly S) | Acly S encourages the activation of pro-inflammatory macrophages and the synthesis of inflammatory mediators | [124] |
Dendritic cells (DCs) | PKM splice isoforms (PKM1 and PKM2) | PTBP1 controls PKM splicing, affecting T cell activation and recruitment | [126] |
|  | CYLD splice variant (sCYLD) | Induces an overactive phenotype in B cells, Treg cells, and DCs, promoting NF-κB activity | |
| Â | CXCL16 variant (CXCL16v) | Secreted to recruit immune cells expressing CXCR6 | [133] |
| Â | DC-CASPIC transcript | Suppresses caspase activity, stimulating NO generation and T cell activation | [134] |
B cells | BCR splice isoforms (ΔIgα and ΔIgβ) | Unable to promote IgM translocation, reducing BCR expression | |
|  | BAFF splice variant (ΔBAFF) | Lowers receptor binding capacity, diminishing BAFF’s ability to stimulate B cells | [139] |
| Â | Pax-5 splice variants (Pax-5a, b, d, e) | Pax-5b and Pax-5e lack part of the DNA binding domain, affecting transcriptional activation of B cell-specific genes | [140] |
| Â | XBP1 splice variant (XBP1-s) | Dual effect on immune regulation | |
T cells | ST2 splice variant (sST2) | Competitively binds to IL-33, blocking IL-33/ST2L signal transduction | |
| Â | CD45 splice isoforms | Differential function in T cell subsets, affecting T cell homeostasis | [153] |
| Â | MALT1 splice variants (MALT1A and MALT1B) | MALT1A increases TCR signal transduction, potentially blocked by hnRNPU | [158] |
|  | IRF1 splice variants (full-length IRF1 and IRF1Δ7) | IRF1Δ7 competes with full-length IRF1, lowering Il12rb1 transcription and IFN-γ expression | [99] |
| Â | mCD137 splice variant (sCD137) | Competitively binds to CD137L, blocking CD137-CD137L signal transduction | |
| Â | FKBP51 splice variant (FKBP51s) | Affects T cell activation and function, as well as promotes Treg transcription and immunosuppressive ability | |
|  | CD247 splicing variants (CD3ι, CD3θand CD3η) | Cause significant harm to T cell development and alter TCR signaling pathways | [167] |
