2026-04-13T02:34:41Zhttps://recercat.cat/oai/requestoai:recercat.cat:2445/2008692025-12-05T12:23:58Zcom_2072_1057col_2072_478916col_2072_478917
RECERCAT
author
Alburquerque Bejar, Juan J.
author
Navajas Chocarro, Pablo
author
Saigí, Maria
author
Ferrero Andrés, Ana
author
Morillas, Juan M.
author
Vilarrubi Porta, Andrea
author
Gomez, Antonio
author
Mate, José L.
author
Munoz Marmol, Ana M.
author
Romero Ferraro, Octavio
author
Blecua, Pedro
author
Davalos, Veronica
author
Esteller, Manel
author
Pros, Eva
author
Llabata, Paula
author
Torres Diz, Manuel
author
Esteve Codina, Anna
author
Sánchez Céspedes, Montserrat
2023-07-19T08:59:52Z2023-07-19T08:59:52Z2023-04-012023-06-20T15:16:37Z
Elucidating the adaptive mechanisms that prevent host immune response in cancer will help predict efficacy of anti-programmed death-1 (PD1)/L1 therapies. Here, we study the cell-intrinsic response of lung cancer (LC) to interferon-y (IFNy), a cytokine that promotes immunoresponse and modulates programmed death-ligand 1 (PD-L1) levels. We report complete refractoriness to IFNy in a subset of LCs as a result of JAK2 or IFNGR1 inactivation. A submaximal response affects another subset that shows constitutive low levels of IFNy-stimulated genes (IySGs) coupled with decreased H3K27ac (histone 3 acetylation at lysine 27) depo-sition and promoter hypermethylation and reduced IFN regulatory factor 1 (IRF1) recruitment to the DNA on IFNy stimulation. Most of these are neuroendocrine small cell LCs (SCLCs) with oncogenic MYC/MYCL1/ MYCN. The oncogenic activation of MYC in SCLC cells downregulates JAK2 and impairs IySGs stimulation by IFNy. MYC amplification tends to associate with a worse response to anti-PD1/L1 therapies. Hence alterations affecting the JAK/STAT pathway and MYC activation prevent stimulation by IFNy and may predict anti-PD1/L1 efficacy in LC.
cc by-nc-nd (c) Alburquerque Bejar, Juan J. et al., 2023 http://creativecommons.org/licenses/by-nc-nd/3.0/es/ info:eu-repo/semantics/openAccess
Càncer de pulmó
Immunoteràpia
Lung cancer
Immunotheraphy
MYC activation impairs cell-intrinsic IFNγ signaling and confers resistance to anti-PD1/PD-L1 therapy in lung cancer
info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion