@article{204206,
  keywords = {Humans, Repressor Proteins, Interferons, Immunotherapy, Triple Negative Breast Neoplasms, Melanoma, Immune Checkpoint Inhibitors, Skin Neoplasms},
  author = {Iv{\'a}n P{\'e}rez-N{\'u}{\~n}ez and Catalina Rozal{\'e}n and Jos{\'e} {\'A}ngel Palomeque and Irene Sangrador and Mariona Dalmau and Laura Comerma and Anna Hern{\'a}ndez-Prat and David Casadevall and Silvia Menendez and Daniel Dan Liu and Minhong Shen and Jordi Berenguer and Irene Rius Ruiz and Raul Pe{\~n}a and Jos{\'e} Carlos Monta{\~n}{\'e}s and Mar Alb{\`a} and Sarah Bonnin and Julia Ponomarenko and Roger Gomis and Juan Miguel Cejalvo and Sonia Servitja and Diego Marzese and Lluis Morey and Leonie Voorwerk and Joaqu{\'\i}n Arribas and Bego{\~n}a Bermejo and Marleen Kok and Lajos Pusztai and Yibin Kang and Joan Albanell and Toni Celi{\`a}-Terrassa},
  title = {LCOR mediates interferon-independent tumor immunogenicity and responsiveness to immune-checkpoint blockade in triple-negative breast cancer},
  abstract = {<p>Ligand-dependent corepressor (LCOR) mediates normal and malignant breast stem cell differentiation. Cancer stem cells (CSCs) generate phenotypic heterogeneity and drive therapy resistance, yet their role in immunotherapy is poorly understood. Here we show that immune-checkpoint blockade (ICB) therapy selects for LCOR CSCs with reduced antigen processing/presentation machinery (APM) driving immune escape and ICB resistance in triple-negative breast cancer (TNBC). We unveil an unexpected function of LCOR as a master transcriptional activator of APM genes binding to IFN-stimulated response elements (ISREs) in an IFN signaling-independent manner. Through genetic modification of LCOR expression, we demonstrate its central role in modulation of tumor immunogenicity and ICB responsiveness. In TNBC, LCOR associates with ICB clinical response. Importantly, extracellular vesicle (EV) Lcor-messenger RNA therapy in combination with anti-PD-L1 overcame resistance and eradicated breast cancer metastasis in preclinical models. Collectively, these data support LCOR as a promising target for enhancement of ICB efficacy in TNBC, by boosting of tumor APM independently of IFN.</p>
},
  year = {2022},
  journal = {Nat Cancer},
  volume = {3},
  pages = {355-370},
  month = {03/2022},
  issn = {2662-1347},
  doi = {10.1038/s43018-022-00339-4},
  language = {eng},
}