Integrative immune transcriptomic classification improves patient selection for precision immunotherapy in advanced gastro-oesophageal adenocarcinoma

综合免疫转录组分类改善晚期胃食管腺癌精准免疫治疗的患者选择

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作者:Manuel Cabeza-Segura #, Valentina Gambardella #, Francisco Gimeno-Valiente, Juan Antonio Carbonell-Asins, Lorena Alarcón-Molero, Arturo González-Vilanova, Sheila Zuñiga-Trejos, Pilar Rentero-Garrido, Rosana Villagrasa, Mireia Gil, Ana Durá, Paula Richart, Noelia Alonso, Marisol Huerta, Susana Rosell

Background

Advanced gastro-oesophageal cancer (GEA) treatment has been improved by the introduction of immune checkpoint inhibitors (CPIs), yet identifying predictive biomarkers remains a priority, particularly in patients with a combined positive score (CPS) < 5, where the benefit is less clear. Our study assesses certain immune microenvironment features related to sensitivity or resistance to CPIs with the

Conclusions

This transcriptomic classification could improve precision immunotherapy for GEA.

Results

This integrative study allowed the identification of four different groups across our patients. Among them, we identified a cluster whose tumours expressed the most gene signatures related to immunomodulatory pathways and immunotherapy response. These tumours presented an enriched immune infiltrate showing high immune function activity that could potentially achieve the best benefit from CPIs. Finally, our findings were proven in an external CPI-exposed population, where the use of our transcriptomic results combined with CPS helped better identify those patients who could benefit from immunotherapy than using CPS alone (p = 0.043). Conclusions: This transcriptomic classification could improve precision immunotherapy for GEA.

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