Alternative splicing (AS) tremendously increases the use of genetic information by generating protein isoforms that differ in protein-protein interactions, catalytic activity and/or subcellular ...localization. This review is not dedicated to AS in general, but rather we focus our attention on AS of P2RX7 pre-mRNA. Whereas P2RX7 mRNA is expressed by virtually all eukaryotic mammalian cells, the expression of this channel receptor is restrained to certain cells. When expressed at the cell membrane, P2RX7 controls downstream events including release of inflammatory molecules, phagocytosis, cell proliferation and death and metabolic events. Therefore, P2RX7 is an important actor of health and diseases. In this review, we summarize the general mechanisms leading to AS. Further, we recapitulate our current knowledge concerning the functional regions in P2RX7, identified at the genetic or exonic levels, and how AS may affect the expression of these regions. Finally, the potential of P2RX7 splice variants to control the fate of cancer cells is discussed.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The emergence of immunotherapy in oncology requires the discovery, validation and subsequent adoption of robust, sensitive and specific predictive and prognostic biomarkers for daily practice. Until ...now, anti-PD-L1 immunohistochemistry (IHC) on tissue sections has been the only validated companion diagnostic test for first-line immunotherapy for advanced and metastatic cancer, notably non-small-cell lung cancer (NSCLC). However, detection of this biomarker presents limitations that have stimulated the development of other biomarkers and other approaches. Within this context, the use of a liquid biopsy (LB) could provide an important complementary or alternative added value to PD-L1 IHC. In this review, we discuss how LBs have been used in the field of immuno-oncology (I-O) to predict response, relapse or adverse advents for patients undergoing immune-checkpoint inhibitor (ICI) therapy (anti-PD-1/PD-L1 and CTLA-4) and we highlight recent developments. Circulating tumor cells (CTCs), cell-free DNA (cfDNA), proteins and cytokines detected in plasma as well as circulating T-lymphocytes are discussed as potential sources for developing new I-O biomarkers. The quantification of cfDNA as a predictive biomarker, as well as its sequencing for the determination of tumor mutational burden, is already well advanced. Additionally, the quantification of PD-L1 from CTCs, bound on exosomes or free in plasma, as well as the determination of cytokines, are also being actively investigated with promising results having recently been published. Lastly, analysis of T-lymphocytes, especially by analyzing the T-cell receptor, has recently emerged as a valuable biomarker that might become relevant for the prediction of response to ICIs. While LBs have not yet been implemented in routine I-O clinical practice, recent promising data and rapidly advancing technologies indicate that this approach has the potential to soon personalize the clinical management of cancer patients receiving ICIs.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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