The Impact of PD-1 Inhibition on Immune-Response to Chemoradiotherapy

Information

  • Research Project
  • 9985855
  • ApplicationId
    9985855
  • Core Project Number
    P20GM103548
  • Full Project Number
    5P20GM103548-10
  • Serial Number
    103548
  • FOA Number
    PAR-13-243
  • Sub Project Id
    5158
  • Project Start Date
    9/2/2011 - 13 years ago
  • Project End Date
    6/30/2021 - 3 years ago
  • Program Officer Name
  • Budget Start Date
    7/1/2020 - 4 years ago
  • Budget End Date
    6/30/2021 - 3 years ago
  • Fiscal Year
    2020
  • Support Year
    10
  • Suffix
  • Award Notice Date
    7/30/2020 - 4 years ago
Organizations

The Impact of PD-1 Inhibition on Immune-Response to Chemoradiotherapy

PROJECT SUMMARY The host immune response is critical for the clearance of head and neck cancer during chemoradiotherapy (CRT). Recent findings suggest impairment of this crucial response during standard CRT. Therefore, to block impairment of the host immune response we have developed a novel chemoimmunotherapy (CIRT) regimen incorporating the PD-1 inhibitor, pembrolizumab. We hypothesize that this novel CIRT regimen will overcome the exhausted immune phenotype evident during standard CRT, thereby facilitating the immune response and enhancing tumor clearance. We will test this hypothesis by comparing the peripheral blood immunocyte response during standard CRT and CIRT. Patient immune phenotype and functional response during treatment will be assessed by flow cytometry, immunocyte immune checkpoint and cytokine expression. In patients with human papilloma virus (HPV) related cancers, retention of the HPV specific immune response will be compared. In addition, we will investigate tumor and tumor microenvironment factors that may impact the host immune response. Pre-treatment tumor infiltrating lymphocyte (TIL) populations, immune checkpoint expression, and immune-related gene signatures will be correlated with clinical outcome and peripheral blood immune response in patients treated with standard CRT and CIRT. In patients who do not respond to treatment, salvage surgical specimens will be evaluated to identify factors that contributed to treatment resistance. With the increasing availability of numerous immunotherapy options, this project will provide important insights into immune biomarkers and identify targets for future therapeutic interventions.

IC Name
NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
  • Activity
    P20
  • Administering IC
    GM
  • Application Type
    5
  • Direct Cost Amount
    178914
  • Indirect Cost Amount
    110032
  • Total Cost
  • Sub Project Total Cost
    288946
  • ARRA Funded
    False
  • CFDA Code
  • Ed Inst. Type
  • Funding ICs
    NIGMS:288946\
  • Funding Mechanism
    RESEARCH CENTERS
  • Study Section
    ZGM1
  • Study Section Name
    Special Emphasis Panel
  • Organization Name
    SANFORD RESEARCH/USD
  • Organization Department
  • Organization DUNS
    050113252
  • Organization City
    SIOUX FALLS
  • Organization State
    SD
  • Organization Country
    UNITED STATES
  • Organization Zip Code
    571040569
  • Organization District
    UNITED STATES