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CXCL9/10-engineered dendritic cells promote T cell activation and enhance immune checkpoint blockade for lung cancer.
Lim, Raymond J; Salehi-Rad, Ramin; Tran, Linh M; Oh, Michael S; Dumitras, Camelia; Crosson, William P; Li, Rui; Patel, Tejas S; Man, Samantha; Yean, Cara E; Abascal, Jensen; Huang, ZiLing; Ong, Stephanie L; Krysan, Kostyantyn; Dubinett, Steven M; Liu, Bin.
Afiliação
  • Lim RJ; Division of Pulmonary and Critical Care, Department of Medicine, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Molecular and Medical Pharmacology, David Geffen School of Medicine at University of California, Los Angeles, Los Angel
  • Salehi-Rad R; Division of Pulmonary and Critical Care, Department of Medicine, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Medicine, VA Greater Los Angeles Healthcare System, Los Angeles, CA 90073, USA.
  • Tran LM; Division of Pulmonary and Critical Care, Department of Medicine, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Medicine, VA Greater Los Angeles Healthcare System, Los Angeles, CA 90073, USA.
  • Oh MS; Division of Hematology and Oncology, Department of Medicine, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, CA 90095, USA; Molecular Biology Institute, University of California, Los Angeles, Los Angeles, CA 90095, USA.
  • Dumitras C; Division of Pulmonary and Critical Care, Department of Medicine, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, CA 90095, USA.
  • Crosson WP; Division of Pulmonary and Critical Care, Department of Medicine, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Molecular and Medical Pharmacology, David Geffen School of Medicine at University of California, Los Angeles, Los Angel
  • Li R; Division of Hematology and Oncology, Department of Medicine, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, CA 90095, USA.
  • Patel TS; Division of Pulmonary and Critical Care, Department of Medicine, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, CA 90095, USA.
  • Man S; Division of Pulmonary and Critical Care, Department of Medicine, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, CA 90095, USA.
  • Yean CE; Division of Pulmonary and Critical Care, Department of Medicine, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, CA 90095, USA.
  • Abascal J; Division of Pulmonary and Critical Care, Department of Medicine, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, CA 90095, USA; Molecular Biology Institute, University of California, Los Angeles, Los Angeles, CA 90095, USA.
  • Huang Z; Division of Pulmonary and Critical Care, Department of Medicine, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, CA 90095, USA.
  • Ong SL; Division of Pulmonary and Critical Care, Department of Medicine, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, CA 90095, USA.
  • Krysan K; Division of Pulmonary and Critical Care, Department of Medicine, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Medicine, VA Greater Los Angeles Healthcare System, Los Angeles, CA 90073, USA.
  • Dubinett SM; Division of Pulmonary and Critical Care, Department of Medicine, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Molecular and Medical Pharmacology, David Geffen School of Medicine at University of California, Los Angeles, Los Angel
  • Liu B; Division of Pulmonary and Critical Care, Department of Medicine, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, CA 90095, USA. Electronic address: bliu@mednet.ucla.edu.
Cell Rep Med ; 5(4): 101479, 2024 Apr 16.
Article em En | MEDLINE | ID: mdl-38518770
ABSTRACT
Immune checkpoint blockade (ICB) with PD-1/PD-L1 inhibition has revolutionized the treatment of non-small cell lung cancer (NSCLC). Durable responses, however, are observed only in a subpopulation of patients. Defective antigen presentation and an immunosuppressive tumor microenvironment (TME) can lead to deficient T cell recruitment and ICB resistance. We evaluate intratumoral (IT) vaccination with CXCL9- and CXCL10-engineered dendritic cells (CXCL9/10-DC) as a strategy to overcome resistance. IT CXCL9/10-DC leads to enhanced T cell infiltration and activation in the TME and tumor inhibition in murine NSCLC models. The antitumor efficacy of IT CXCL9/10-DC is dependent on CD4+ and CD8+ T cells, as well as CXCR3-dependent T cell trafficking from the lymph node. IT CXCL9/10-DC, in combination with ICB, overcomes resistance and establishes systemic tumor-specific immunity in murine models. These studies provide a mechanistic understanding of CXCL9/10-DC-mediated host immune activation and support clinical translation of IT CXCL9/10-DC to augment ICB efficacy in NSCLC.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Carcinoma Pulmonar de Células não Pequenas / Neoplasias Pulmonares Limite: Animals / Humans Idioma: En Revista: Cell Rep Med Ano de publicação: 2024 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Carcinoma Pulmonar de Células não Pequenas / Neoplasias Pulmonares Limite: Animals / Humans Idioma: En Revista: Cell Rep Med Ano de publicação: 2024 Tipo de documento: Article