Triggering receptor expressed on myeloid cells 2 (TREM-2), a glycosylated receptor belonging to the immunoglobin superfamily and especially expressed in the myeloid cell lineage, is frequently explained as a reminiscent receptor for both adaptive and innate immunity regulation. TREM-2 is also acknowledged to influence NK cell differentiation via the PI3K and PLCγ signaling pathways, as well as the partial activation or direct inhibition of T cells. Additionally, TREM-2 overexpression is substantially linked to cell-specific functions, such as enhanced phagocytosis, reduced toll-like receptor (TLR)-mediated inflammatory cytokine production, increased transcription of anti-inflammatory cytokines, and reshaped T cell function. Whereas TREM-2-deficient cells exhibit diminished phagocytic function and enhanced proinflammatory cytokines production, proceeding to inflammatory injuries and an immunosuppressive environment for disease progression. Despite the growing literature supporting TREM-2+ cells in various diseases, such as neurodegenerative disorders and cancer, substantial facets of TREM-2-mediated signaling remain inadequately understood relevant to pathophysiology conditions. In this direction, herein, we have summarized the current knowledge on TREM-2 biology and cell-specific TREM-2 expression, particularly in the modulation of pivotal TREM-2-dependent functions under physiopathological conditions. Furthermore, molecular regulation and generic biological relevance of TREM-2 are also discussed, which might provide an alternative approach for preventing or reducing TREM-2-associated deformities. At last, we discussed the TREM-2 function in supporting an immunosuppressive cancer environment and as a potential drug target for cancer immunotherapy. Hence, summarized knowledge of TREM-2 might provide a window to overcome challenges in clinically effective therapies for TREM-2-induced diseases in humans.
- MeSH
- buňky NK imunologie MeSH
- fagocytóza MeSH
- lidé MeSH
- membránové glykoproteiny * metabolismus genetika MeSH
- nádory imunologie metabolismus genetika MeSH
- přirozená imunita MeSH
- receptory imunologické * metabolismus genetika MeSH
- signální transdukce MeSH
- T-lymfocyty imunologie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Non-small cell lung cancer (NSCLC) is largely promoted by a multistep tumorigenesis process involving various genetic and epigenetic alterations, which essentially contribute to the high incidence of mortality among patients with NSCLC. Clinical observations revealed that NSCLC also co-opts a multifaceted immune checkpoint dysregulation as an important driving factor in NSCLC progression and development. For example, a deregulated PI3K/AKT/mTOR pathway has been noticed in 50-70% of NSCLC cases, primarily modulated by mutations in key oncogenes such as ALK, EGFR, KRAS, and others. Additionally, genetic association studies containing patient-specific factors and local reimbursement criteria expose/reveal mutations in EGFR/ALK/ROS/BRAF/KRAS/PD-L1 proteins to determine the suitability of available immunotherapy or tyrosine kinase inhibitor therapy. Thus, the expression of such checkpoints on tumors and immune cells is pivotal in understanding the therapeutic efficacy and has been extensively studied for NSCLC treatments. Therefore, this review summarizes current knowledge in NSCLC tumorigenesis, focusing on its genetic and epigenetic intricacies, immune checkpoint dysregulation, and the evolving landscape of targeted therapies. In the context of current and future therapies, we emphasize the significance of antibodies targeting PD-1/PD-L1 and CTLA-4 interactions as the primary therapeutic strategy for immune system reactivation in NSCLC. Other approaches involving the promising potential of nanobodies, probodies, affibodies, and DARPINs targeting immune checkpoints are also described; these are under active research or clinical trials to mediate immune regulation and reduce cancer progression. This comprehensive review underscores the multifaceted nature, current state and future directions of NSCLC research and treatment.
- MeSH
- antigeny CD274 metabolismus MeSH
- erbB receptory metabolismus MeSH
- fosfatidylinositol-3-kinasy metabolismus MeSH
- karcinogeneze MeSH
- lidé MeSH
- nádorová transformace buněk MeSH
- nádory plic * farmakoterapie genetika MeSH
- nemalobuněčný karcinom plic * farmakoterapie genetika MeSH
- protoonkogenní proteiny p21(ras) MeSH
- tyrosinkinasové receptory metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
