Immune profiling of gastric adenocarcinomas in EU and LATAM countries identifies global differences in immune subgroups and microbiome influence
Por:
van Schooten T, Cabeza-Segura M, Ferreira R, Martínez-Ciarpaglini C, Barros R, Santos-Antunes J, Costa A, Fernández-Figueroa E, Lino-Silva L, Hernandez-Guerrero A, Ruiz-García E, Caballero C, Boggino H, Gauna C, Cantero D, Freile B, Esteso F, O'Connor J, Riquelme A, Owen G, Riquelme E, Roa J, Latorre G, Garrido M, Ruiz-Pace F, García M, Alsina M, Lordick F, Farrés J, Carbonell-Asins J, Villagrasa R, Pereira R, Pouw R, Jimenez-Marti E, Miralles A, Dientsmann R, Figueiredo C, Carneiro F, Cervantes A, Derks S, Fleitas T
Publicada:
18 may 2025
Ahead of Print:
1 mar 2025
Resumen:
BackgroundGastric 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.MethodsTumor 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.ResultsImmune 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.DiscussionBoth 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.
Filiaciones:
van Schooten T:
Amsterdam Univ Med Ctr UMC Locat Vrije Univ Amster, Dept Med Oncol, Amsterdam, Netherlands
Canc Ctr Amsterdam, Canc Biol & Immunol, Amsterdam, Netherlands
Oncode Inst, Amsterdam, Netherlands
Cabeza-Segura M:
Univ Valencia, Hosp Clin Univ, Biomed Res Inst, Dept Med Oncol,INCLIVA, Valencia, Spain
Ferreira R:
Univ Porto, I3S Inst Invest & Inovacao Saude, Porto, Portugal
Univ Porto, Ipatimup Inst Mol Pathol & Immunol, Porto, Portugal
Martínez-Ciarpaglini C:
Hosp Clin Univ Valencia, Pathol Dept, Incliva, Valencia, Spain
Barros R:
Univ Porto, I3S Inst Invest & Inovacao Saude, Porto, Portugal
Univ Porto, Ipatimup Inst Mol Pathol & Immunol, Porto, Portugal
Univ Porto, Fac Med, Porto, Portugal
Unidade Local Saude Sao Joao, Dept Pathol, Porto, Portugal
Santos-Antunes J:
Unidade Local Saude Sao Joao, Dept Gastroenterol, Porto, Portugal
Costa A:
Unidade Local Saude Sao Joao, Dept Oncol, Porto, Portugal
Fernández-Figueroa E:
Inst Nacl Med Genom, Nucleo Innovac Med Precis B, Ciudad De Mexico, Mexico
Lino-Silva L:
Natl Canc Inst INCan, Surg Pathol, Mexico City, Mexico
Hernandez-Guerrero A:
Inst Nacl Cancerol, Dept Gastrointestinal Endoscopy, Mexico City, Mexico
Ruiz-García E:
Inst Nacl Cancerol, Dept Tumores Tubo Digest, Ciudad De Mexico, Mexico
Inst Nacl Cancerol, Lab Med Traslac, Ciudad De Mexico, Mexico
Caballero C:
GENPAT, Dept Pathol, Asuncion, Paraguay
Boggino H:
GENPAT, Dept Pathol, Asuncion, Paraguay
Gauna C:
Inst Previs Social, Med Oncol Dept, Asuncion, Paraguay
Cantero D:
Inst Previs Social, Dept Gastroenterol, Asuncion, Paraguay
Freile B:
Inst Alexander Fleming, Med Oncol Dept, Buenos Aires, Argentina
Esteso F:
Inst Alexander Fleming, Med Oncol Dept, Buenos Aires, Argentina
O'Connor J:
Inst Alexander Fleming, Med Oncol Dept, Buenos Aires, Argentina
Riquelme A:
Pontificia Univ Catolica Chile, Fac Med, Ctr Prevent & Control Canc CECAN, Dept Gastroenterol, Santiago, Chile
Owen G:
Pontificia Univ Catolica Chile, Millennium Inst Immunol & Immunotherapy, Fac Biol Sci, Ctr Prevent & Control Canc CECAN,Adv Ctr Chron Dis, Santiago, Chile
Riquelme E:
Pontificia Univ Catolica Chile, Fac Med, Dept Resp Dis, Santiago, Chile
Roa J:
Pontificia Univ Catolica Chile, Fac Med, Dept Pathol, Santiago, Chile
Latorre G:
Pontificia Univ Catolica Chile, Fac Med, Dept Gastroenterol, Santiago, Chile
Garrido M:
Univ Mayor, Fac Ciencia Salud, Ctr Oncol Precis, Huechuraba, Chile
Ruiz-Pace F:
Vall DHebron Inst Oncol, Oncol Data Sci, Barcelona, Spain
García M:
Vall dHebron Inst Oncol, Med Oncol Dept, Barcelona, Spain
Alsina M:
Vall dHebron Inst Oncol, Med Oncol Dept, Barcelona, Spain
Hosp Univ Navarra, Navarrabiomed IdiSNA, Pamplona, Spain
Lordick F:
Univ Leipzig, Comprehens Canc Ctr Cent Germany CCCG, Med Ctr, Dept Med Oncol Gastroenterol Hepatol & Pulmonol 2, Leipzig, Germany
Farrés J:
Anax Biotech SL, Barcelona, Spain
Carbonell-Asins J:
INCLIVA Biomed Res Inst, Dept Bioestat, Valencia, Spain
Villagrasa R:
Hosp Clin Univ Valencia, Dept Gastroenterol, Valencia, Spain
Pereira R:
Inst Previs Social, Dept Gastroenterol, Asuncion, Paraguay
Pouw R:
Amsterdam UMC, Gastroenterol Dept, Amsterdam, Netherlands
Jimenez-Marti E:
Univ Valencia, Hosp Clin Univ, Biomed Res Inst, Dept Med Oncol,INCLIVA, Valencia, Spain
Miralles A:
Univ Valencia, Hosp Clin Univ, Biomed Res Inst, Dept Med Oncol,INCLIVA, Valencia, Spain
Dientsmann R:
Vall DHebron Inst Oncol, Oncol Data Sci, Barcelona, Spain
Figueiredo C:
Univ Porto, I3S Inst Invest & Inovacao Saude, Porto, Portugal
Univ Porto, Ipatimup Inst Mol Pathol & Immunol, Porto, Portugal
Unidade Local Saude Sao Joao, Dept Pathol, Porto, Portugal
Carneiro F:
Univ Porto, I3S Inst Invest & Inovacao Saude, Porto, Portugal
Univ Porto, Ipatimup Inst Mol Pathol & Immunol, Porto, Portugal
Univ Porto, Fac Med, Porto, Portugal
Unidade Local Saude Sao Joao, Dept Pathol, Porto, Portugal
Cervantes A:
Univ Valencia, Hosp Clin Univ, Biomed Res Inst, Dept Med Oncol,INCLIVA, Valencia, Spain
CiberOnc Carlos III Inst, Madrid, Spain
Derks S:
Amsterdam Univ Med Ctr UMC Locat Vrije Univ Amster, Dept Med Oncol, Amsterdam, Netherlands
Canc Ctr Amsterdam, Canc Biol & Immunol, Amsterdam, Netherlands
Oncode Inst, Amsterdam, Netherlands
Fleitas T:
Univ Valencia, Hosp Clin Univ, Biomed Res Inst, Dept Med Oncol,INCLIVA, Valencia, Spain
Green Submitted, hybrid
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