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High systemic and tumor-associated IL-8 correlates with reduced clinical benefit of PD-L1 blockade.
Yuen, Kobe C; Liu, Li-Fen; Gupta, Vinita; Madireddi, Shravan; Keerthivasan, Shilpa; Li, Congfen; Rishipathak, Deepali; Williams, Patrick; Kadel, Edward E; Koeppen, Hartmut; Chen, Ying-Jiun; Modrusan, Zora; Grogan, Jane L; Banchereau, Romain; Leng, Ning; Thastrom, AnnChristine; Shen, Xiadong; Hashimoto, Kenji; Tayama, Darren; van der Heijden, Michiel S; Rosenberg, Jonathan E; McDermott, David F; Powles, Thomas; Hegde, Priti S; Huseni, Mahrukh A; Mariathasan, Sanjeev.
Afiliación
  • Yuen KC; Genentech, San Francisco, CA, USA.
  • Liu LF; Genentech, San Francisco, CA, USA.
  • Gupta V; Genentech, San Francisco, CA, USA.
  • Madireddi S; Genentech, San Francisco, CA, USA.
  • Keerthivasan S; Genentech, San Francisco, CA, USA.
  • Li C; Genentech, San Francisco, CA, USA.
  • Rishipathak D; Genentech, San Francisco, CA, USA.
  • Williams P; Genentech, San Francisco, CA, USA.
  • Kadel EE; Genentech, San Francisco, CA, USA.
  • Koeppen H; Genentech, San Francisco, CA, USA.
  • Chen YJ; Genentech, San Francisco, CA, USA.
  • Modrusan Z; Genentech, San Francisco, CA, USA.
  • Grogan JL; Genentech, San Francisco, CA, USA.
  • Banchereau R; Genentech, San Francisco, CA, USA.
  • Leng N; Genentech, San Francisco, CA, USA.
  • Thastrom A; Genentech, San Francisco, CA, USA.
  • Shen X; Genentech, San Francisco, CA, USA.
  • Hashimoto K; Roche Products Ltd., Welwyn Garden City, UK.
  • Tayama D; Genentech, San Francisco, CA, USA.
  • van der Heijden MS; Netherlands Cancer Institute, Amsterdam, the Netherlands.
  • Rosenberg JE; Genitourinary Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
  • McDermott DF; Beth Israel Deaconess Medical Center, Boston, MA, USA.
  • Powles T; Barts Experimental Cancer Medicine Centre, Barts Cancer Institute, Queen Mary University of London, London, UK.
  • Hegde PS; Genentech, San Francisco, CA, USA.
  • Huseni MA; Genentech, San Francisco, CA, USA. huseni.mahrukh@gene.com.
  • Mariathasan S; Genentech, San Francisco, CA, USA. mariathasan.sanjeev@gene.com.
Nat Med ; 26(5): 693-698, 2020 05.
Article en En | MEDLINE | ID: mdl-32405063
Although elevated plasma interleukin-8 (pIL-8) has been associated with poor outcome to immune checkpoint blockade 1, this has not been comprehensively evaluated in large randomized studies. Here we analyzed circulating pIL-8 and IL8 gene expression in peripheral blood mononuclear cells and tumors of patients treated with atezolizumab (anti-PD-L1 monoclonal antibody) from multiple randomized trials representing 1,445 patients with metastatic urothelial carcinoma (mUC) and metastatic renal cell carcinoma. High levels of IL-8 in plasma, peripheral blood mononuclear cells and tumors were associated with decreased efficacy of atezolizumab in patients with mUC and metastatic renal cell carcinoma, even in tumors that were classically CD8+ T cell inflamed. Low baseline pIL-8 in patients with mUC was associated with increased response to atezolizumab and chemotherapy. Patients with mUC who experienced on-treatment decreases in pIL-8 exhibited improved overall survival when treated with atezolizumab but not with chemotherapy. Single-cell RNA sequencing of the immune compartment showed that IL8 is primarily expressed in circulating and intratumoral myeloid cells and that high IL8 expression is associated with downregulation of the antigen-presentation machinery. Therapies that can reverse the impacts of IL-8-mediated myeloid inflammation will be essential for improving outcomes of patients treated with immune checkpoint inhibitors.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Interleucina-8 / Antígeno B7-H1 / Antineoplásicos Inmunológicos / Neoplasias Tipo de estudio: Clinical_trials / Diagnostic_studies / Prognostic_studies / Risk_factors_studies Idioma: En Revista: Nat Med Asunto de la revista: BIOLOGIA MOLECULAR / MEDICINA Año: 2020 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Interleucina-8 / Antígeno B7-H1 / Antineoplásicos Inmunológicos / Neoplasias Tipo de estudio: Clinical_trials / Diagnostic_studies / Prognostic_studies / Risk_factors_studies Idioma: En Revista: Nat Med Asunto de la revista: BIOLOGIA MOLECULAR / MEDICINA Año: 2020 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos