Your browser doesn't support javascript.
loading
Monocytic MDSCs exhibit superior immune suppression via adenosine and depletion of adenosine improves efficacy of immunotherapy.
Sarkar, Omar S; Donninger, Howard; Al Rayyan, Numan; Chew, Lewis C; Stamp, Bryce; Zhang, Xiang; Whitt, Aaron; Li, Chi; Hall, Melissa; Mitchell, Robert A; Zippelius, Alfred; Eaton, John; Chesney, Jason A; Yaddanapudi, Kavitha.
Afiliación
  • Sarkar OS; Department of Microbiology and Immunology, University of Louisville, Louisville, KY, USA.
  • Donninger H; Department of Medicine, University of Louisville, Louisville, KY, USA.
  • Al Rayyan N; James Graham Brown Cancer Center, University of Louisville, Louisville, KY, USA.
  • Chew LC; Experimental Therapeutics Program, University of Louisville, Louisville, KY, USA.
  • Stamp B; Department of Medicine, University of Louisville, Louisville, KY, USA.
  • Zhang X; James Graham Brown Cancer Center, University of Louisville, Louisville, KY, USA.
  • Whitt A; Natural Agricultural Research Center, P.O. Box 639, Baq'a 19381, Jordan.
  • Li C; James Graham Brown Cancer Center, University of Louisville, Louisville, KY, USA.
  • Hall M; James Graham Brown Cancer Center, University of Louisville, Louisville, KY, USA.
  • Mitchell RA; Department of Chemistry, University of Louisville, Louisville, KY, USA.
  • Zippelius A; Department of Pharmacology and Toxicology, University of Louisville, Louisville, KY, USA.
  • Eaton J; Department of Medicine, University of Louisville, Louisville, KY, USA.
  • Chesney JA; James Graham Brown Cancer Center, University of Louisville, Louisville, KY, USA.
  • Yaddanapudi K; Experimental Therapeutics Program, University of Louisville, Louisville, KY, USA.
Sci Adv ; 9(26): eadg3736, 2023 06 30.
Article en En | MEDLINE | ID: mdl-37390211
Immune checkpoint inhibitor (ICI) therapy is effective against many cancers for a subset of patients; a large percentage of patients remain unresponsive to this therapy. One contributing factor to ICI resistance is accumulation of monocytic myeloid-derived suppressor cells (M-MDSCs), a subset of innate immune cells with potent immunosuppressive activity against T lymphocytes. Here, using lung, melanoma, and breast cancer mouse models, we show that CD73-expressing M-MDSCs in the tumor microenvironment (TME) exhibit superior T cell suppressor function. Tumor-derived PGE2, a prostaglandin, directly induces CD73 expression in M-MDSCs via both Stat3 and CREB. The resulting CD73 overexpression induces elevated levels of adenosine, a nucleoside with T cell-suppressive activity, culminating in suppression of antitumor CD8+ T cell activity. Depletion of adenosine in the TME by the repurposed drug PEGylated adenosine deaminase (PEG-ADA) increases CD8+ T cell activity and enhances response to ICI therapy. Use of PEG-ADA can therefore be a therapeutic option to overcome resistance to ICIs in cancer patients.
Asunto(s)
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: Células Supresoras de Origen Mieloide Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Sci Adv Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos 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: Células Supresoras de Origen Mieloide Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Sci Adv Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos