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Engineered Immunologic Niche Monitors Checkpoint Blockade Response and Probes Mechanisms of Resistance.
Raghani, Ravi M; Urie, Russell R; Ma, Jeffrey A; Escalona, Guillermo; Schrack, Ian A; DiLillo, Katarina M; Kandagatla, Pridvi; Decker, Joseph T; Morris, Aaron H; Arnold, Kelly B; Jeruss, Jacqueline S; Shea, Lonnie D.
Afiliación
  • Raghani RM; Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan.
  • Urie RR; Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan.
  • Ma JA; Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan.
  • Escalona G; Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan.
  • Schrack IA; Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan.
  • DiLillo KM; Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan.
  • Kandagatla P; Department of Surgery, Washington University, St. Louis, Missouri.
  • Decker JT; Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan.
  • Morris AH; Department of Cariology, Restorative Sciences, and Endodontics, University of Michigan, Ann Arbor, Michigan.
  • Arnold KB; Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan.
  • Jeruss JS; Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan.
  • Shea LD; Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan.
Immunomedicine ; 4(1)2024 Jun.
Article en En | MEDLINE | ID: mdl-39246390
ABSTRACT
Antibodies to programmed cell death protein1 (anti-PD-1) have become a promising immunotherapy for triple negative breast cancer (TNBC), blocking PD-L1 signaling from pro-tumor cells through T cell PD-1 receptor binding. Nevertheless, only 10-20% of PD-L1+ metastatic TNBC patients who meet criteria benefit from ICB, and biomarkers to predict patient response have been elusive. We have previously developed an immunological niche, consisting of a microporous implant in the subcutaneous space, that supports tissue formation whose immune composition is consistent with that within vital organs. Herein, we investigated dynamic gene expression within this immunological niche to provide biomarkers of response to anti-PD-1. In a 4T1 model of metastatic TNBC, we observed sensitivity and resistance to anti-PD-1 based on primary tumor growth and survival. The niche was biopsied before, during, and after anti-PD-1 therapy, and analyzed for cell types and gene expression indicative of treatment refractivity. Myeloid cell-to-lymphocyte ratios were altered between ICB-sensitivity and resistance. Longitudinal analysis of gene expression implicated dynamic myeloid cell function that stratified sensitivity from resistance. A niche-derived gene signature predicted sensitivity or resistance prior to therapy. Analysis of the niche to monitor immunotherapy response presents a new opportunity to personalize care and investigate mechanisms underlying treatment resistance.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Immunomedicine Año: 2024 Tipo del documento: Article Pais de publicación: Alemania
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Immunomedicine Año: 2024 Tipo del documento: Article Pais de publicación: Alemania