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CD8+ T cells maintain killing of MHC-I-negative tumor cells through the NKG2D-NKG2DL axis.
Lerner, Emily C; Woroniecka, Karolina I; D'Anniballe, Vincent M; Wilkinson, Daniel S; Mohan, Aditya A; Lorrey, Selena J; Waibl-Polania, Jessica; Wachsmuth, Lucas P; Miggelbrink, Alexandra M; Jackson, Joshua D; Cui, Xiuyu; Raj, Jude A; Tomaszewski, William H; Cook, Sarah L; Sampson, John H; Patel, Anoop P; Khasraw, Mustafa; Gunn, Michael D; Fecci, Peter E.
Afiliación
  • Lerner EC; Duke University School of Medicine, Durham, NC, USA.
  • Woroniecka KI; Department of Biomedical Engineering, Duke University, Durham, NC, USA.
  • D'Anniballe VM; Department of Pathology, Duke University Medical Center, Durham, NC, USA.
  • Wilkinson DS; Duke University School of Medicine, Durham, NC, USA.
  • Mohan AA; Preston Robert Tisch Brain Tumor Center, Duke University Medical Center, Durham, NC, USA.
  • Lorrey SJ; Department of Neurosurgery, Duke University Medical Center, Durham, NC, USA.
  • Waibl-Polania J; Department of Neurosurgery, Duke University Medical Center, Durham, NC, USA.
  • Wachsmuth LP; Department of Immunology, Duke University Medical Center, Durham, NC, USA.
  • Miggelbrink AM; Department of Pathology, Duke University Medical Center, Durham, NC, USA.
  • Jackson JD; Duke University School of Medicine, Durham, NC, USA.
  • Cui X; Department of Pathology, Duke University Medical Center, Durham, NC, USA.
  • Raj JA; Department of Pathology, Duke University Medical Center, Durham, NC, USA.
  • Tomaszewski WH; Department of Neurosurgery, Duke University Medical Center, Durham, NC, USA.
  • Cook SL; Department of Neurosurgery, Duke University Medical Center, Durham, NC, USA.
  • Sampson JH; Duke University School of Medicine, Durham, NC, USA.
  • Patel AP; Department of Immunology, Duke University Medical Center, Durham, NC, USA.
  • Khasraw M; Preston Robert Tisch Brain Tumor Center, Duke University Medical Center, Durham, NC, USA.
  • Gunn MD; Department of Neurosurgery, Duke University Medical Center, Durham, NC, USA.
  • Fecci PE; Preston Robert Tisch Brain Tumor Center, Duke University Medical Center, Durham, NC, USA.
Nat Cancer ; 4(9): 1258-1272, 2023 09.
Article en En | MEDLINE | ID: mdl-37537301
The accepted paradigm for both cellular and anti-tumor immunity relies upon tumor cell killing by CD8+ T cells recognizing cognate antigens presented in the context of target cell major histocompatibility complex (MHC) class I (MHC-I) molecules. Likewise, a classically described mechanism of tumor immune escape is tumor MHC-I downregulation. Here, we report that CD8+ T cells maintain the capacity to kill tumor cells that are entirely devoid of MHC-I expression. This capacity proves to be dependent instead on interactions between T cell natural killer group 2D (NKG2D) and tumor NKG2D ligands (NKG2DLs), the latter of which are highly expressed on MHC-loss variants. Necessarily, tumor cell killing in these instances is antigen independent, although prior T cell antigen-specific activation is required and can be furnished by myeloid cells or even neighboring MHC-replete tumor cells. In this manner, adaptive priming can beget innate killing. These mechanisms are active in vivo in mice as well as in vitro in human tumor systems and are obviated by NKG2D knockout or blockade. These studies challenge the long-advanced notion that downregulation of MHC-I is a viable means of tumor immune escape and instead identify the NKG2D-NKG2DL axis as a therapeutic target for enhancing T cell-dependent anti-tumor immunity against MHC-loss variants.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Linfocitos T CD8-positivos / Neoplasias Límite: Animals / Humans Idioma: En Revista: Nat Cancer Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido
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: Linfocitos T CD8-positivos / Neoplasias Límite: Animals / Humans Idioma: En Revista: Nat Cancer Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido