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LIF regulates CXCL9 in tumor-associated macrophages and prevents CD8+ T cell tumor-infiltration impairing anti-PD1 therapy

Author

Listed:
  • Mónica Pascual-García

    (Vall d’Hebron University Hospital
    CIBERONC)

  • Ester Bonfill-Teixidor

    (Vall d’Hebron University Hospital
    CIBERONC)

  • Ester Planas-Rigol

    (Vall d’Hebron University Hospital)

  • Carlota Rubio-Perez

    (Vall d’Hebron University Hospital)

  • Raffaella Iurlaro

    (Vall d’Hebron University Hospital)

  • Alexandra Arias

    (Vall d’Hebron University Hospital)

  • Isabel Cuartas

    (Vall d’Hebron University Hospital)

  • Ada Sala-Hojman

    (Vall d’Hebron University Hospital)

  • Laura Escudero

    (Vall d’Hebron University Hospital)

  • Francisco Martínez-Ricarte

    (Vall d’Hebron University Hospital
    Universitat Autònoma de Barcelona)

  • Isabel Huber-Ruano

    (Vall d’Hebron University Hospital)

  • Paolo Nuciforo

    (Vall d’Hebron University Hospital)

  • Leire Pedrosa

    (University of Barcelona and Institut d’Investigació Biomèdica August Pi i Sunyer (IDIBAPS))

  • Carolina Marques

    (Spanish National Cancer Research Center, CNIO)

  • Irene Braña

    (Vall d’Hebron University Hospital)

  • Elena Garralda

    (Vall d’Hebron University Hospital)

  • María Vieito

    (Vall d’Hebron University Hospital)

  • Massimo Squatrito

    (Spanish National Cancer Research Center, CNIO)

  • Estela Pineda

    (University of Barcelona and Institut d’Investigació Biomèdica August Pi i Sunyer (IDIBAPS))

  • Francesc Graus

    (University of Barcelona and Institut d’Investigació Biomèdica August Pi i Sunyer (IDIBAPS))

  • Carmen Espejo

    (Vall d’Hebron University Hospital
    Universitat Autònoma de Barcelona)

  • Juan Sahuquillo

    (Vall d’Hebron University Hospital
    Universitat Autònoma de Barcelona)

  • Josep Tabernero

    (Vall d’Hebron University Hospital
    CIBERONC
    Universitat Autònoma de Barcelona)

  • Joan Seoane

    (Vall d’Hebron University Hospital
    CIBERONC
    Universitat Autònoma de Barcelona
    Institució Catalana de Recerca i Estudis Avançats (ICREA))

Abstract

Cancer response to immunotherapy depends on the infiltration of CD8+ T cells and the presence of tumor-associated macrophages within tumors. Still, little is known about the determinants of these factors. We show that LIF assumes a crucial role in the regulation of CD8+ T cell tumor infiltration, while promoting the presence of protumoral tumor-associated macrophages. We observe that the blockade of LIF in tumors expressing high levels of LIF decreases CD206, CD163 and CCL2 and induces CXCL9 expression in tumor-associated macrophages. The blockade of LIF releases the epigenetic silencing of CXCL9 triggering CD8+ T cell tumor infiltration. The combination of LIF neutralizing antibodies with the inhibition of the PD1 immune checkpoint promotes tumor regression, immunological memory and an increase in overall survival.

Suggested Citation

  • Mónica Pascual-García & Ester Bonfill-Teixidor & Ester Planas-Rigol & Carlota Rubio-Perez & Raffaella Iurlaro & Alexandra Arias & Isabel Cuartas & Ada Sala-Hojman & Laura Escudero & Francisco Martínez, 2019. "LIF regulates CXCL9 in tumor-associated macrophages and prevents CD8+ T cell tumor-infiltration impairing anti-PD1 therapy," Nature Communications, Nature, vol. 10(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-10369-9
    DOI: 10.1038/s41467-019-10369-9
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