Your browser doesn't support javascript.
loading
Neutrophil content predicts lymphocyte depletion and anti-PD1 treatment failure in NSCLC.
Kargl, Julia; Zhu, Xiaodong; Zhang, Huajia; Yang, Grace H Y; Friesen, Travis J; Shipley, Melissa; Maeda, Dean Y; Zebala, John A; McKay-Fleisch, Jill; Meredith, Gavin; Mashadi-Hossein, Afshin; Baik, Christina; Pierce, Robert H; Redman, Mary W; Thompson, Jeffrey C; Albelda, Steven M; Bolouri, Hamid; Houghton, A McGarry.
Afiliación
  • Kargl J; Fred Hutchinson Clinical Research Division, Seattle, Washington, USA.
  • Zhu X; Otto Loewi Research Center, Division of Pharmacology, Medical University of Graz, Graz, Austria.
  • Zhang H; Fred Hutchinson Clinical Research Division, Seattle, Washington, USA.
  • Yang GHY; Fred Hutchinson Clinical Research Division, Seattle, Washington, USA.
  • Friesen TJ; Fred Hutchinson Clinical Research Division, Seattle, Washington, USA.
  • Shipley M; Fred Hutchinson Clinical Research Division, Seattle, Washington, USA.
  • Maeda DY; Fred Hutchinson Clinical Research Division, Seattle, Washington, USA.
  • Zebala JA; Syntrix Pharmaceuticals, Auburn, Washington, USA.
  • McKay-Fleisch J; Syntrix Pharmaceuticals, Auburn, Washington, USA.
  • Meredith G; Nanostring Inc., Seattle, Washington, USA.
  • Mashadi-Hossein A; Nanostring Inc., Seattle, Washington, USA.
  • Baik C; Nanostring Inc., Seattle, Washington, USA.
  • Pierce RH; Fred Hutchinson Clinical Research Division, Seattle, Washington, USA.
  • Redman MW; Fred Hutchinson Clinical Research Division, Seattle, Washington, USA.
  • Thompson JC; Fred Hutchinson Clinical Research Division, Seattle, Washington, USA.
  • Albelda SM; Division of Pulmonary, Allergy, and Critical Care Medicine, Thoracic Oncology Group, Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA.
  • Bolouri H; Division of Pulmonary, Allergy, and Critical Care Medicine, Thoracic Oncology Group, Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA.
  • Houghton AM; Human Biology Division, Fred Hutchinson Cancer Research Division, Seattle, Washington, USA.
JCI Insight ; 4(24)2019 12 19.
Article en En | MEDLINE | ID: mdl-31852845
Immune checkpoint inhibitor (ICI) treatment has recently become a first-line therapy for many non-small cell lung cancer (NSCLC) patients. Unfortunately, most NSCLC patients are refractory to ICI monotherapy, and initial attempts to address this issue with secondary therapeutics have proven unsuccessful. To identify entities precluding CD8+ T cell accumulation in this process, we performed unbiased analyses on flow cytometry, gene expression, and multiplexed immunohistochemical data from a NSCLC patient cohort. The results revealed the presence of a myeloid-rich subgroup, which was devoid of CD4+ and CD8+ T cells. Of all myeloid cell types assessed, neutrophils were the most highly associated with the myeloid phenotype. Additionally, the ratio of CD8+ T cells to neutrophils (CD8/PMN) within the tumor mass optimally distinguished between active and myeloid cases. This ratio was also capable of showing the separation of patients responsive to ICI therapy from those with stable or progressive disease in 2 independent cohorts. Tumor-bearing mice treated with a combination of anti-PD1 and SX-682 (CXCR1/2 inhibitor) displayed relocation of lymphocytes from the tumor periphery into a malignant tumor, which was associated with induction of IFN-γ-responsive genes. These results suggest that neutrophil antagonism may represent a viable secondary therapeutic strategy to enhance ICI treatment outcomes.
Asunto(s)
Palabras clave
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Linfocitos Infiltrantes de Tumor / Carcinoma de Pulmón de Células no Pequeñas / Antineoplásicos Inmunológicos / Neoplasias Pulmonares / Neutrófilos Tipo de estudio: Etiology_studies / Incidence_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Límite: Aged / Animals / Female / Humans / Male / Middle aged Idioma: En Revista: JCI Insight Año: 2019 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Linfocitos Infiltrantes de Tumor / Carcinoma de Pulmón de Células no Pequeñas / Antineoplásicos Inmunológicos / Neoplasias Pulmonares / Neutrófilos Tipo de estudio: Etiology_studies / Incidence_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Límite: Aged / Animals / Female / Humans / Male / Middle aged Idioma: En Revista: JCI Insight Año: 2019 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos