| Literature DB >> 35121837 |
Daniel Ajona1,2,3,4, Sergio Ortiz-Espinosa5,6, Teresa Lozano7,8, Francisco Exposito5,7,9,10, Alfonso Calvo5,7,9,10, Karmele Valencia5,7,9,6, Miriam Redrado5,7, Ana Remírez5, Fernando Lecanda5,7,9,10, Diego Alignani7,9,11, Juan J Lasarte7,8, Irati Macaya5,7, Yaiza Senent5, Cristina Bértolo5,7,9, Cristina Sainz5,7,9, Ignacio Gil-Bazo5,7,9,12, Iñaki Eguren-Santamaría12, Jose M Lopez-Picazo7,9,12, Alvaro Gonzalez7,6,13, Jose L Perez-Gracia7,9,12, Carlos E de Andrea7,9,10,14, Silvestre Vicent5,7,9, Miguel F Sanmamed7,9,8,12, Luis M Montuenga5,7,9,10, Ruben Pio5,7,9,6.
Abstract
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.Entities:
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Year: 2020 PMID： 35121837 DOI： 10.1038/s43018-019-0007-9
Source DB: PubMed Journal: Nat Cancer ISSN： 2662-1347