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CD4+ T cells drive an inflammatory, TNF-α/IFN-rich tumor microenvironment responsive to chemotherapy.
Tilsed, Caitlin M; Principe, Nicola; Kidman, Joel; Chin, Wee Loong; Orozco Morales, M Lizeth; Zemek, Rachael M; Chee, Jonathan; Islam, Rasa; Fear, Vanessa S; Forbes, Catherine; Aston, Wayne J; Jansen, Maud; Chopra, Abha; Lassmann, Timo; Nowak, Anna K; Fisher, Scott A; Lake, Richard A; Lesterhuis, W Joost.
Afiliación
  • Tilsed CM; National Centre for Asbestos Related Diseases, Nedlands, WA 6009, Australia; School of Biomedical Sciences, University of Western Australia, Crawley, WA 6009, Australia; Institute for Respiratory Health, Perth, WA 6101, Australia.
  • Principe N; National Centre for Asbestos Related Diseases, Nedlands, WA 6009, Australia; School of Biomedical Sciences, University of Western Australia, Crawley, WA 6009, Australia; Institute for Respiratory Health, Perth, WA 6101, Australia.
  • Kidman J; National Centre for Asbestos Related Diseases, Nedlands, WA 6009, Australia; School of Biomedical Sciences, University of Western Australia, Crawley, WA 6009, Australia; Institute for Respiratory Health, Perth, WA 6101, Australia.
  • Chin WL; National Centre for Asbestos Related Diseases, Nedlands, WA 6009, Australia; Medical School, University of Western Australia, Crawley, WA 6009, Australia; Department of Medical Oncology, Sir Charles Gairdner Hospital, Nedlands, WA 6009, Australia.
  • Orozco Morales ML; National Centre for Asbestos Related Diseases, Nedlands, WA 6009, Australia; School of Biomedical Sciences, University of Western Australia, Crawley, WA 6009, Australia; Institute for Respiratory Health, Perth, WA 6101, Australia; Telethon Kids Institute, University of Western Australia, West Perth,
  • Zemek RM; Telethon Kids Institute, University of Western Australia, West Perth, WA 6872, Australia.
  • Chee J; National Centre for Asbestos Related Diseases, Nedlands, WA 6009, Australia; School of Biomedical Sciences, University of Western Australia, Crawley, WA 6009, Australia; Institute for Respiratory Health, Perth, WA 6101, Australia.
  • Islam R; National Centre for Asbestos Related Diseases, Nedlands, WA 6009, Australia.
  • Fear VS; Telethon Kids Institute, University of Western Australia, West Perth, WA 6872, Australia.
  • Forbes C; Telethon Kids Institute, University of Western Australia, West Perth, WA 6872, Australia.
  • Aston WJ; National Centre for Asbestos Related Diseases, Nedlands, WA 6009, Australia.
  • Jansen M; National Centre for Asbestos Related Diseases, Nedlands, WA 6009, Australia.
  • Chopra A; Institute of Immunology and Infectious Diseases, Murdoch University, Murdoch, WA 6150, Australia.
  • Lassmann T; Telethon Kids Institute, University of Western Australia, West Perth, WA 6872, Australia.
  • Nowak AK; National Centre for Asbestos Related Diseases, Nedlands, WA 6009, Australia; Institute for Respiratory Health, Perth, WA 6101, Australia; Medical School, University of Western Australia, Crawley, WA 6009, Australia; Department of Medical Oncology, Sir Charles Gairdner Hospital, Nedlands, WA 6009, Au
  • Fisher SA; National Centre for Asbestos Related Diseases, Nedlands, WA 6009, Australia; School of Biomedical Sciences, University of Western Australia, Crawley, WA 6009, Australia; Institute for Respiratory Health, Perth, WA 6101, Australia.
  • Lake RA; National Centre for Asbestos Related Diseases, Nedlands, WA 6009, Australia; School of Biomedical Sciences, University of Western Australia, Crawley, WA 6009, Australia; Institute for Respiratory Health, Perth, WA 6101, Australia.
  • Lesterhuis WJ; National Centre for Asbestos Related Diseases, Nedlands, WA 6009, Australia; School of Biomedical Sciences, University of Western Australia, Crawley, WA 6009, Australia; Institute for Respiratory Health, Perth, WA 6101, Australia; Telethon Kids Institute, University of Western Australia, West Perth,
Cell Rep ; 41(13): 111874, 2022 12 27.
Article en En | MEDLINE | ID: mdl-36577370
While chemotherapy remains the first-line treatment for many cancers, it is still unclear what distinguishes responders from non-responders. Here, we characterize the chemotherapy-responsive tumor microenvironment in mice, using RNA sequencing on tumors before and after cyclophosphamide, and compare the gene expression profiles of responders with progressors. Responsive tumors have an inflammatory and highly immune infiltrated pre-treatment tumor microenvironment characterized by the enrichment of pathways associated with CD4+ T cells, interferons (IFNs), and tumor necrosis factor alpha (TNF-α). The same gene expression profile is associated with response to cyclophosphamide-based chemotherapy in patients with breast cancer. Finally, we demonstrate that tumors can be sensitized to cyclophosphamide and 5-FU chemotherapy by pre-treatment with recombinant TNF-α, IFNγ, and poly(I:C). Thus, a CD4+ T cell-inflamed pre-treatment tumor microenvironment is necessary for response to chemotherapy, and this state can be therapeutically attained by targeted immunotherapy.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Linfocitos T / Neoplasias Límite: Animals Idioma: En Revista: Cell Rep Año: 2022 Tipo del documento: Article País de afiliación: Australia Pais de publicación: 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: Linfocitos T / Neoplasias Límite: Animals Idioma: En Revista: Cell Rep Año: 2022 Tipo del documento: Article País de afiliación: Australia Pais de publicación: Estados Unidos