Dissecting genetic and immune drivers of heterogeneous responses to neoadjuvant immunochemotherapy in gastric cancer - PubMed
2 days ago
- #multi-omics
- #immunochemotherapy
- #gastric cancer
- Neoadjuvant immunochemotherapy (nICT) improves gastric cancer (GC) outcomes, but resistance remains a challenge.
- Study analyzes 110 GC patients from NEOSUMMIT-01 trial using multi-omic sequencing and functional validation.
- Identifies five tumor microenvironment ecotypes (EC1-5) linked to therapy response.
- nICT achieves response in EC1 (T cell activation), EC2 (tertiary lymphoid structures), and EC3 (vascular normalization).
- nICT resistance observed in EC4 (extracellular matrix organization) and EC5 (immunosuppressive macrophage enrichment).
- Resistance in EC5 mediated by interaction between APOA1+ tumor cells and TREM2+ macrophages.
- Multiple biomarkers associated with nICT efficacy identified, including SBS19, HLA-B��15:02, FDXR expression, and FGFR pathway activity.
- Provides a multi-omic stratification model for treatment response-based patient stratification.
- Study offers mechanistic insights into nICT in GC, informs therapeutic decisions, and reveals potential targets.