Journal: Pharmaceutical Science Advances

Article Title: Mechanisms of tumor cell evasion from NK cell-mediated killing and advances in NK cell-based cancer immunotherapy

doi: 10.1016/j.pscia.2026.100109

Figure Lengend Snippet: Factors influencing the exhausted state of NK cells. The exhaustion of NK cells in the TME is regulated by multiple factors which results in NK cell function impairment due to: the downregulated expression of NK cell-activating receptors (e.g., NKG2D, DNAM-1, NKp30), the reduced secretion of effector cytokines (such as IFN-γ), and the upregulated expression of immunosuppressive molecules (e.g., PD-1, NKG2A, TIGIT, CD96, TIM-3, LAG-3). Additionally, transforming growth factor-β (TGF-β) secreted by tumor cells, cancer-associated fibroblasts (CAFs), and extracellular vesicles (EVs); hypoxic microenvironment; indoleamine 2,3-dioxygenase (IDO); prostaglandin E2 (PGE2); and immunosuppressive cells including macrophages, regulatory T cells (Treg), and myeloid-derived suppressor cells (MDSC) are involved in regulating NK cell exhaustion through multiple pathways.

Article Snippet: TIM-3 ligands-including Galectin-9, PS, HMGB1, and CEACAM-1-play crucial roles in regulating NK activity.

Techniques: Cell Function Assay, Expressing, Derivative Assay

Journal: Pharmaceutical Science Advances

Article Title: Mechanisms of tumor cell evasion from NK cell-mediated killing and advances in NK cell-based cancer immunotherapy

doi: 10.1016/j.pscia.2026.100109

Figure Lengend Snippet: Strategies for enhancing NK cell anti-tumor activity. The anti-tumor efficacy of NK cells can be improved through multiple approaches: Adoptive NK cell infusions, including autologous NK cells (combined with HAIC), allogeneic NK cells (with high potential), and infusions with or without allogeneic transplantation; NK cell checkpoint inhibitors targeting molecules such as PD-1/PD-L1, KIRs (KIR2DL1/2/3/5), NKG2A/CD94, TIM-3, and LAG-3; Advanced applications of CAR-NK cells, including IL-15-secreting CAR-NK cell therapy targeting mesothelin, TIPE2 gene-knockout CAR-NK therapy, and application of modified CCCR-NK92; Administration of stimulatory cytokines like IL-2, IL-15, IL-18, and IL-21; Bi or trispecific killer engagers, including Bispecific antibody: LB1410 (anti-PD-1/TIM-3) and trispecific nanobody: PDL1/PD-1/NKG2A.

Article Snippet: TIM-3 ligands-including Galectin-9, PS, HMGB1, and CEACAM-1-play crucial roles in regulating NK activity.

Techniques: Activity Assay, Transplantation Assay, Gene Knockout, Modification