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Determinants of gastric cancer immune escape identified from non-coding immune-landscape quantitative trait loci.
Miliotis, Christos; Ma, Yuling; Katopodi, Xanthi-Lida; Karagkouni, Dimitra; Kanata, Eleni; Mattioli, Kaia; Kalavros, Nikolas; Pita-Juárez, Yered H; Batalini, Felipe; Ramnarine, Varune R; Nanda, Shivani; Slack, Frank J; Vlachos, Ioannis S.
Afiliación
  • Miliotis C; Harvard Medical School Initiative for RNA Medicine, Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
  • Ma Y; Harvard Program in Virology, Harvard University Graduate School of Arts and Sciences, Boston, MA, USA.
  • Katopodi XL; Harvard Medical School Initiative for RNA Medicine, Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
  • Karagkouni D; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Kanata E; Harvard Medical School Initiative for RNA Medicine, Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
  • Mattioli K; Harvard Medical School Initiative for RNA Medicine, Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
  • Kalavros N; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Pita-Juárez YH; Cancer Center & Cancer Research Institute, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
  • Batalini F; Harvard Medical School Initiative for RNA Medicine, Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
  • Ramnarine VR; Harvard Medical School Initiative for RNA Medicine, Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
  • Nanda S; Division of Genetics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
  • Slack FJ; Harvard Medical School Initiative for RNA Medicine, Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
  • Vlachos IS; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Nat Commun ; 15(1): 4319, 2024 May 21.
Article en En | MEDLINE | ID: mdl-38773080
ABSTRACT
The landscape of non-coding mutations in cancer progression and immune evasion is largely unexplored. Here, we identify transcrptome-wide somatic and germline 3' untranslated region (3'-UTR) variants from 375 gastric cancer patients from The Cancer Genome Atlas. By performing gene expression quantitative trait loci (eQTL) and immune landscape QTL (ilQTL) analysis, we discover 3'-UTR variants with cis effects on expression and immune landscape phenotypes, such as immune cell infiltration and T cell receptor diversity. Using a massively parallel reporter assay, we distinguish between causal and correlative effects of 3'-UTR eQTLs in immune-related genes. Our approach identifies numerous 3'-UTR eQTLs and ilQTLs, providing a unique resource for the identification of immunotherapeutic targets and biomarkers. A prioritized ilQTL variant signature predicts response to immunotherapy better than standard-of-care PD-L1 expression in independent patient cohorts, showcasing the untapped potential of non-coding mutations in cancer.
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Neoplasias Gástricas / Escape del Tumor / Regiones no Traducidas 3' / Sitios de Carácter Cuantitativo Límite: Female / Humans / Male Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Neoplasias Gástricas / Escape del Tumor / Regiones no Traducidas 3' / Sitios de Carácter Cuantitativo Límite: Female / Humans / Male Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos