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Short-term starvation reduces IGF-1 levels to sensitize lung tumors to PD-1 immune checkpoint blockade.
Ajona, Daniel; Ortiz-Espinosa, Sergio; Lozano, Teresa; Exposito, Francisco; Calvo, Alfonso; Valencia, Karmele; Redrado, Miriam; Remírez, Ana; Lecanda, Fernando; Alignani, Diego; Lasarte, Juan J; Macaya, Irati; Senent, Yaiza; Bértolo, Cristina; Sainz, Cristina; Gil-Bazo, Ignacio; Eguren-Santamaría, Iñaki; Lopez-Picazo, Jose M; Gonzalez, Alvaro; Perez-Gracia, Jose L; de Andrea, Carlos E; Vicent, Silvestre; Sanmamed, Miguel F; Montuenga, Luis M; Pio, Ruben.
Afiliación
  • Ajona D; Program in Solid Tumors, Center for Applied Medical Research (CIMA), University of Navarra, Pamplona, Spain. dajonama@unav.es.
  • Ortiz-Espinosa S; Navarra Institute for Health Research (IdISNA), Pamplona, Spain. dajonama@unav.es.
  • Lozano T; Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Madrid, Spain. dajonama@unav.es.
  • Exposito F; Department of Biochemistry and Genetics, School of Sciences, University of Navarra, Pamplona, Spain. dajonama@unav.es.
  • Calvo A; Program in Solid Tumors, Center for Applied Medical Research (CIMA), University of Navarra, Pamplona, Spain.
  • Valencia K; Department of Biochemistry and Genetics, School of Sciences, University of Navarra, Pamplona, Spain.
  • Redrado M; Navarra Institute for Health Research (IdISNA), Pamplona, Spain.
  • Remírez A; Program in Immunology and Immunotherapy, CIMA, University of Navarra, Pamplona, Spain.
  • Lecanda F; Program in Solid Tumors, Center for Applied Medical Research (CIMA), University of Navarra, Pamplona, Spain.
  • Alignani D; Navarra Institute for Health Research (IdISNA), Pamplona, Spain.
  • Lasarte JJ; Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Madrid, Spain.
  • Macaya I; Department of Pathology, Anatomy and Physiology, School of Medicine, University of Navarra, Pamplona, Spain.
  • Senent Y; Program in Solid Tumors, Center for Applied Medical Research (CIMA), University of Navarra, Pamplona, Spain.
  • Bértolo C; Navarra Institute for Health Research (IdISNA), Pamplona, Spain.
  • Sainz C; Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Madrid, Spain.
  • Gil-Bazo I; Department of Pathology, Anatomy and Physiology, School of Medicine, University of Navarra, Pamplona, Spain.
  • Eguren-Santamaría I; Program in Solid Tumors, Center for Applied Medical Research (CIMA), University of Navarra, Pamplona, Spain.
  • Lopez-Picazo JM; Navarra Institute for Health Research (IdISNA), Pamplona, Spain.
  • Gonzalez A; Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Madrid, Spain.
  • Perez-Gracia JL; Department of Biochemistry and Genetics, School of Sciences, University of Navarra, Pamplona, Spain.
  • de Andrea CE; Program in Solid Tumors, Center for Applied Medical Research (CIMA), University of Navarra, Pamplona, Spain.
  • Vicent S; Navarra Institute for Health Research (IdISNA), Pamplona, Spain.
  • Sanmamed MF; Program in Solid Tumors, Center for Applied Medical Research (CIMA), University of Navarra, Pamplona, Spain.
  • Montuenga LM; Program in Solid Tumors, Center for Applied Medical Research (CIMA), University of Navarra, Pamplona, Spain.
  • Pio R; Navarra Institute for Health Research (IdISNA), Pamplona, Spain.
Nat Cancer ; 1(1): 75-85, 2020 01.
Article en En | MEDLINE | ID: mdl-35121837
Harnessing the immune system by blocking the programmed cell death protein 1 (PD-1) pathway has been a major breakthrough in non-small-cell lung cancer treatment. Nonetheless, many patients fail to respond to PD-1 inhibition. Using three syngeneic models, we demonstrate that short-term starvation synergizes with PD-1 blockade to inhibit lung cancer progression and metastasis. This antitumor activity was linked to a reduction in circulating insulin-like growth factor 1 (IGF-1) and a downregulation of IGF-1 receptor (IGF-1R) signaling in tumor cells. A combined inhibition of IGF-1R and PD-1 synergistically reduced tumor growth in mice. This effect required CD8 cells, boosted the intratumoral CD8/Treg ratio and led to the development of tumor-specific immunity. In patients with non-small-cell lung cancer, high plasma levels of IGF-1 or high IGF-1R expression in tumors was associated with resistance to anti-PD-1-programmed death-ligand 1 immunotherapy. In conclusion, our data strongly support the clinical evaluation of IGF-1 modulators in combination with PD-1 blockade.
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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 Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: Nat Cancer Año: 2020 Tipo del documento: Article País de afiliación: España Pais de publicación: Reino Unido
Texto completo
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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 Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: Nat Cancer Año: 2020 Tipo del documento: Article País de afiliación: España Pais de publicación: Reino Unido