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Background <p>Gastric cancer (GC) patients from European (EU) and especially Latin American (LATAM) countries are underrepresented in previous large-scale multi-omic studies that have identified clinically relevant subgroups. The LEGACY study aimed to profile the molecular and immunological features of GCs from EU and LATAM countries.</p> Methods <p>Tumor biopsies from 95 EU and 56 LATAM GCs were profiled with immunohistochemistry (CD3, CD8, FOXP3, PD-L1, MSI and HER2), Nanostring mRNA expression analyses, and microbiome sequencing.</p> Results <p>Immune profiling identified four distinct immune clusters: a T cell dominant cluster with enriched activation pathways, a macrophage dominant cluster and an immune excluded microenvironment which were equally distributed among the countries. A fourth cluster of mostly Mexican patients consisted of excessive T cell numbers accompanied by enhanced cytokine signaling in absence of enhanced antigen presentation and cytotoxicity signatures and a strong association with <i>H. pylori</i> infection.</p> Discussion <p>Both EU and LATAM countries have GCs with a T cell inflamed microenvironment that might benefit from checkpoint inhibition. We identified a highly inflamed GC subgroup that lacked antigen presentation and cytotoxicity associated with <i>H. pylori</i> CagA-positive strains, suggesting their contribution to tumor immune tolerance. Future studies are needed to unravel whether these cancers benefit from immunotherapy as well.</p>

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Immune profiling of gastric adenocarcinomas in EU and LATAM countries identifies global differences in immune subgroups and microbiome influence

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年3月20日

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  • Tessa S. Groen – van Schooten,
  • Manuel Cabeza-Segura,
  • Rui M. Ferreira,
  • Carolina Martínez-Ciarpaglini,
  • Rita Barros,
  • João Santos-Antunes,
  • Andreia Costa,
  • Edith A. Fernández-Figueroa,
  • Leonardo Lino-Silva,
  • Angélica Ixtaccihuatl Hernandez-Guerrero,
  • Erika Ruiz-García,
  • Carmelo Caballero,
  • Hugo Boggino,
  • Cinthia Gauna,
  • Daniel Cantero,
  • Berenice Freile,
  • Federico Esteso,
  • Juan O´Connor,
  • Arnoldo Riquelme,
  • Gareth Owen,
  • Erick Riquelme,
  • Juan Carlos Roa,
  • Gonzalo Latorre,
  • Marcelo Garrido,
  • Fiorella Ruiz-Pace,
  • Marc Diez García,
  • Maria Alsina,
  • Florian Lordick,
  • Judith Farrés,
  • Juan Antonio Carbonell-Asins,
  • Rossana Villagrasa,
  • Rita Pereira,
  • Roos E. Pouw,
  • Elena Jimenez-Martí,
  • Ana Miralles,
  • Rodrigo Dientsmann,
  • Ceu Figueiredo,
  • Fatima Carneiro,
  • Andrés Cervantes,
  • Sarah Derks,
  • Tania Fleitas

摘要

Background

Gastric cancer (GC) patients from European (EU) and especially Latin American (LATAM) countries are underrepresented in previous large-scale multi-omic studies that have identified clinically relevant subgroups. The LEGACY study aimed to profile the molecular and immunological features of GCs from EU and LATAM countries.

Methods

Tumor biopsies from 95 EU and 56 LATAM GCs were profiled with immunohistochemistry (CD3, CD8, FOXP3, PD-L1, MSI and HER2), Nanostring mRNA expression analyses, and microbiome sequencing.

Results

Immune profiling identified four distinct immune clusters: a T cell dominant cluster with enriched activation pathways, a macrophage dominant cluster and an immune excluded microenvironment which were equally distributed among the countries. A fourth cluster of mostly Mexican patients consisted of excessive T cell numbers accompanied by enhanced cytokine signaling in absence of enhanced antigen presentation and cytotoxicity signatures and a strong association with H. pylori infection.

Discussion

Both EU and LATAM countries have GCs with a T cell inflamed microenvironment that might benefit from checkpoint inhibition. We identified a highly inflamed GC subgroup that lacked antigen presentation and cytotoxicity associated with H. pylori CagA-positive strains, suggesting their contribution to tumor immune tolerance. Future studies are needed to unravel whether these cancers benefit from immunotherapy as well.