ESTRO 2024 - Abstract Book

S434

Clinical - Biomarkers

ESTRO 2024

91

Digital Poster

Comprehensive molecular analysis of pyroptosis in gastric cancer cells for antitumor immunotherapy

You-Xin Gao, Li-Li Shen, Xin-Peng Yang

Fujian Medical University Union Hospital, Department of Gastric Surgery, Fuzhou, China

Purpose/Objective:

Pyroptosis plays a crucial role in the immune response. However, the effect of pyroptosis on tumor microenvironment remodeling and immunotherapy of gastric cancer (GC) is still unclear.

Material/Methods:

GEO large sample data (GSE15459, GSE54129, and GSE62254) were used to explore the immunoregulatory role of pyroptosis. TCGA cohort was used to elucidate multiple molecular events associated with pyroptosis, and a pyroptosis risk score (PRS) was constructed. The prognostic performance of PRS was validated in postoperative GC samples from three public databases (n=925) and four independent Chinese medical cohorts (n=977). Single cell sequencing and multicolor immunofluorescence were used to elucidate the immune infiltration landscape associated with PRS. GC patients receiving neoadjuvant immunotherapy (n=48) and GC patients receiving neoadjuvant chemotherapy alone (n=49) were enrolled to explore the value of PRS in neoadjuvant immunotherapy. Western blot and FACS methods were used to clarify the specific mechanism of BATF2 and PTPRJ in PRS regulating pyroptosis.

Results:

GC pyroptosis participates in immune activation in the tumor microenvironment and plays a powerful anti-tumor immune role. The PRS composed of four pyroptosis DEGs (BATF2, PTPRJ, RGS1, VCAN) was a reliable and independent biomarker of GC. PRSlow was associated with an activated pyroptosis pathway and a greater infiltration of anti-tumor immune cells, including more Effector T cells and CD4+ T cells, and with the polarization of tumor-associated macrophages in tumor center. Importantly, PRSlow marks the effectiveness of neoadjuvant immunotherapy and enables screening of GC patients in CPS≥1 who benefit from neoadjuvant therapy. In addition, BATF2 and PTPRJ, the key tumor suppressor molecules in PRS, affect the drug resistance of GC cells by activating GSDME-related pyroptosis pathway.

Conclusion:

In summary, our study demonstrated that pyroptosis activates anti-tumor immune processes in the tumor microenvironment. The constructed PRS can be used as an effective quantitative tool for pyroptosis analysis to guide more effective immunotherapy strategies for GC patients.

Keywords: pyroptosis, neoadjuvant immunotherapy, scRNA