NCR3LG1 (Natural Killer Cell Cytotoxicity Receptor 3 Ligand 1)

Recent advances in NK cell-based immunotherapies-such as cytokine modulation, adoptive NK transfer, and checkpoint blockade-have demonstrated potential to reverse NK exhaustion and enhance antitumor efficacy. In this review, we systematically dissect the molecular and cellular pathways underlying NK cell suppression in ovarian cancer and evaluate emerging strategies to reinvigorate NK-mediated immunosurveillance.

P1, N=97, Recruiting, Boehringer Ingelheim | N=70 --> 97

Following cell co-culture, the ERK phosphorylation level in NK cells was gradually increased with the up-regulation of B7-H6. B7-H6 may enhance the killing capacity of NK cells by activating the NKp30 downstream ERK signaling pathway.

P1, N=70, Recruiting, Boehringer Ingelheim | Trial completion date: Dec 2027 --> Sep 2028 | Trial primary completion date: Sep 2027 --> Jun 2028

Using peripheral blood biomarkers, we characterized immune subtypes of osteosarcoma, and developed a predictive model for metastasis. These biomarkers may serve as potential therapeutic targets for future immunotherapy.

P1, N=70, Recruiting, Boehringer Ingelheim | Trial completion date: Feb 2027 --> Dec 2027 | Trial primary completion date: Nov 2026 --> Sep 2027

Combination therapy with B7-H6M4-LC21 (10 mg/kg) and B7-H6M18/IL-15/IL-15Ra sushi (0.03 mg/kg) achieved synergistic tumor inhibition (p<0.05), surpassing the efficacy of T cell-based combinations. These findings establish B7-H6-targeted BsAbs combined with cytokine engineering as a viable strategy for treating refractory solid tumors.

Our findings suggest that the combination of BCL-2 mutant-expressing B7H6-targeting CAR-T cells and venetoclax could be a promising novel strategy against B7H6-expressing SCLCs and other solid tumors, providing the foundation for CAR-T cells and proapoptotic small molecules therapy in patients with SCLCs in a clinical trial.

Taken together, SNRPA promotes HCC growth and lenvatinib resistance via B7-H6-STAT3/AKT axis through facilitating B7-H6 pre-mRNA maturation by maintaining its intron 2 splicing. Thus, SNRPA may be a promising target for HCC therapy and lenvatinib resistance reversion.

This review explores the structural characteristics, receptor-ligand interactions, and signaling pathways associated with each B7-H family member. We also discuss the family's impact on tumor immunity and potential therapeutic strategies.

Importantly, intratumoral B7-H6+ neutrophils increased with tumor progression and predicted poor patient survival. Our results illuminate a novel mechanism of B7-H6 expression on tumor-activated neutrophils in GC, and also suggest B7-H6+ neutrophils would be novel potential biomarkers in GC.