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Mutational landscape influences immunotherapy outcomes among patients with non-small-cell lung cancer with human leukocyte antigen supertype B44.
Cummings, Amy L; Gukasyan, Jaklin; Lu, Henry Y; Grogan, Tristan; Sunga, Gemalene; Fares, Charlene M; Hornstein, Nicholas; Zaretsky, Jesse; Carroll, James; Bachrach, Benjamin; Akingbemi, Wisdom O; Li, Debory; Noor, Zorawar; Lisberg, Aaron; Goldman, Jonathan W; Elashoff, David; Bui, Alex A T; Ribas, Antoni; Dubinett, Steven M; Rossetti, Maura; Garon, Edward B.
Afiliación
  • Cummings AL; Department of Medicine, David Geffen School of Medicine at the University of California, Los Angeles, Los Angeles, CA, USA.
  • Gukasyan J; Department of Medicine, David Geffen School of Medicine at the University of California, Los Angeles, Los Angeles, CA, USA.
  • Lu HY; Department of Medicine, David Geffen School of Medicine at the University of California, Los Angeles, Los Angeles, CA, USA.
  • Grogan T; Department of Medicine, David Geffen School of Medicine at the University of California, Los Angeles, Los Angeles, CA, USA.
  • Sunga G; Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at the University of California, Los Angeles, Los Angeles, CA, USA.
  • Fares CM; Department of Medicine, David Geffen School of Medicine at the University of California, Los Angeles, Los Angeles, CA, USA.
  • Hornstein N; Department of Medicine, David Geffen School of Medicine at the University of California, Los Angeles, Los Angeles, CA, USA.
  • Zaretsky J; Department of Medicine, David Geffen School of Medicine at the University of California, Los Angeles, Los Angeles, CA, USA.
  • Carroll J; Department of Medicine, David Geffen School of Medicine at the University of California, Los Angeles, Los Angeles, CA, USA.
  • Bachrach B; Department of Medicine, David Geffen School of Medicine at the University of California, Los Angeles, Los Angeles, CA, USA.
  • Akingbemi WO; Department of Medicine, David Geffen School of Medicine at the University of California, Los Angeles, Los Angeles, CA, USA.
  • Li D; Department of Medicine, David Geffen School of Medicine at the University of California, Los Angeles, Los Angeles, CA, USA.
  • Noor Z; Department of Medicine, David Geffen School of Medicine at the University of California, Los Angeles, Los Angeles, CA, USA.
  • Lisberg A; Department of Medicine, David Geffen School of Medicine at the University of California, Los Angeles, Los Angeles, CA, USA.
  • Goldman JW; Department of Medicine, David Geffen School of Medicine at the University of California, Los Angeles, Los Angeles, CA, USA.
  • Elashoff D; Department of Medicine, David Geffen School of Medicine at the University of California, Los Angeles, Los Angeles, CA, USA.
  • Bui AAT; Department of Radiology, David Geffen School of Medicine at the University of California, Los Angeles, Los Angeles, CA, USA.
  • Ribas A; Department of Medicine, David Geffen School of Medicine at the University of California, Los Angeles, Los Angeles, CA, USA.
  • Dubinett SM; Department of Medicine, David Geffen School of Medicine at the University of California, Los Angeles, Los Angeles, CA, USA.
  • Rossetti M; Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at the University of California, Los Angeles, Los Angeles, CA, USA.
  • Garon EB; Department of Medicine, David Geffen School of Medicine at the University of California, Los Angeles, Los Angeles, CA, USA. egaron@mednet.ucla.edu.
Nat Cancer ; 1(12): 1167-1175, 2020 12.
Article en En | MEDLINE | ID: mdl-35121931
ABSTRACT
Human leukocyte antigen (HLA)-B has been recognized as a major determinant of discrepancies in disease outcomes, and recent evidence indicates a role in immune checkpoint blockade (ICB) efficacy. The B44 supertype, which features an electropositive binding pocket that preferentially displays peptides with negatively charged amino acid anchors, is associated with improved survival in ICB-treated melanoma. Yet this effect was not seen in ICB-treated non-small-cell lung cancer (NSCLC). Here we show that mutations leading to glutamic acid substitutions occur more often in melanoma than NSCLC based on mutational landscape. We additionally show stratifying B44 based on the presence of somatic mutations that lead to negatively charged glutamic acid anchors identifies patients with NSCLC with an ICB benefit similar to that seen in melanoma. We anticipate these findings could improve assessment of HLA-related outcomes and prediction of ICB benefit in those with B44, representing approximately half of the world's population.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Carcinoma de Pulmón de Células no Pequeñas / Neoplasias Pulmonares / Melanoma Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: Nat Cancer Año: 2020 Tipo del documento: Article País de afiliación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Carcinoma de Pulmón de Células no Pequeñas / Neoplasias Pulmonares / Melanoma Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: Nat Cancer Año: 2020 Tipo del documento: Article País de afiliación: Estados Unidos