<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT02980146</url>
  </required_header>
  <id_info>
    <org_study_id>RC16_0212</org_study_id>
    <nct_id>NCT02980146</nct_id>
  </id_info>
  <brief_title>Impact of HLA-E Overexpression by Tumor Cells on the Biology of TIL in Colorectal Cancer</brief_title>
  <acronym>HLA-E CCR</acronym>
  <official_title>Correlation Between HLA-E Overexpression by Tumor Cells and the Biology of Tumor-infiltrating Lymphocytes Depending on the Microsatellite Status in Colorectal Cancer.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Nantes University Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>U892 INSERM Team 3</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Nantes University Hospital</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Accumulating evidences suggest that colorectal cancer (CRC) progression is not solely&#xD;
      determined by the genetic abnormalities of the tumor cells but also by the host response.&#xD;
      Indeed, recent studies in CRC have associated improved survival with a high number of&#xD;
      tumor-infiltrating (TIL) memory and cytotoxic T lymphocytes, suggesting a link between tumor&#xD;
      progression and in situ T cell response. Gene expression profiling studies have clearly&#xD;
      isolated a well-known subgroup of CRC characterized by microsatellite instability (MSI) CRC,&#xD;
      associated with a strong immune response signature involving both Th1/cytotoxic and immune&#xD;
      evasion pathways. Moreover, the investigators have previously shown that HLA-E/β2m is&#xD;
      overexpressed by tumor cells in roughly 20% of CRC and is associated with a worse prognosis,&#xD;
      most likely due to NK and T effector cell functions upon engagement with the inhibitory NK&#xD;
      receptor CD94/NKG2A. However, our recent results on an enlarger cohort of patients suggest&#xD;
      that if this observation holds true for MSS CRC, HLA-E over-expression is inversely&#xD;
      associated with a good prognosis in MSI CRC. Thus, the phenotype and function of TIL,&#xD;
      depending on the MSI/MSS status of CRC have to be precised. The investigators hypothesized&#xD;
      that in MSI CRC, known to express a high number of MSI-H related frameshift peptides which&#xD;
      represent a pool of tumor specific antigens, HLA-E could present peptides to TCR of non&#xD;
      conventional CD8+ HLA-E-restricted alpha-betaT cells (also expressing CD94), then inducing a&#xD;
      strong antitumor cytolytic activity. Therefore, the aim of this project is to determine the&#xD;
      exact phenotype, function and specificity of the CD94+ TIL in CRC, depending on both the&#xD;
      HLA-E and the MSI/MSS status of tumor cells. These results could impact the clinical practice&#xD;
      as anti-NKG2A monoclonal antibodies or frameshift peptide based immunotherapy that could be&#xD;
      promising new therapeutic options in CRC patients.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>June 1, 2016</start_date>
  <completion_date type="Actual">June 26, 2017</completion_date>
  <primary_completion_date type="Actual">June 26, 2017</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>The phenotype of TIL will be precised by immunohistochemisry and flow cytometry using various combinations of monoclonal antibodies to identify different subset of TIL and their frequency, especially those expressing NKG2A or NKG2C chain.</measure>
    <time_frame>Until 5 years</time_frame>
  </primary_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Actual">28</enrollment>
  <condition>ColoRectal Cancer</condition>
  <arm_group>
    <arm_group_label>Group &quot;patients with colorectal cancer&quot;</arm_group_label>
    <description>Major patients treated surgically for colorectal cancer at Nantes University Hospital or at the Institut de Cancerologie de l'Ouest and agreeing to participate in the study</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Non interventional study</intervention_name>
    <arm_group_label>Group &quot;patients with colorectal cancer&quot;</arm_group_label>
  </intervention>
  <biospec_retention>Samples Without DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      20 mL of Blood, a tumor fragment and a fragment of colonic mucosa&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Major patients treated surgically for colorectal cancer at the Nantes University Hospital&#xD;
        or the West Institute of Cancerology&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Major patients treated surgically for colorectal cancer at the Nantes University&#xD;
             Hospital or the West Institute of Cancerology&#xD;
&#xD;
          -  Patients agreeing to participate in the study&#xD;
&#xD;
        Non inclusion Criteria:&#xD;
&#xD;
          -  Age&gt; 85 years&#xD;
&#xD;
          -  Neoadjuvant or immunosuppressive therapy for other pathology&#xD;
&#xD;
          -  Size of the tumor insufficient to carry out all the samples dedicated to the research&#xD;
             without constraining the diagnostic step (tumoral sampling at least equal to 1 cm3)&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>85 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Céline BOSSARD, Pr</last_name>
    <role>Principal Investigator</role>
    <affiliation>Nantes University Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Nantes University Hospital</name>
      <address>
        <city>Nantes</city>
        <zip>44093</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <verification_date>April 2019</verification_date>
  <study_first_submitted>November 21, 2016</study_first_submitted>
  <study_first_submitted_qc>November 29, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 2, 2016</study_first_posted>
  <last_update_submitted>April 17, 2019</last_update_submitted>
  <last_update_submitted_qc>April 17, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">April 18, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Colorectal Neoplasms</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT02980146
org study id: RC16_0212
nct id: NCT02980146
lead sponsor: 
collaborator: 
has dmc: No
Accumulating evidences suggest that colorectal cancer (CRC) progression is not solely
      determined by the genetic abnormalities of the tumor cells but also by the host response.
      Indeed, recent studies in CRC have associated improved survival with a high number of
      tumor-infiltrating (TIL) memory and cytotoxic T lymphocytes, suggesting a link between tumor
      progression and in situ T cell response. Gene expression profiling studies have clearly
      isolated a well-known subgroup of CRC characterized by microsatellite instability (MSI) CRC,
      associated with a strong immune response signature involving both Th1/cytotoxic and immune
      evasion pathways. Moreover, the investigators have previously shown that HLA-E/β2m is
      overexpressed by tumor cells in roughly 20% of CRC and is associated with a worse prognosis,
      most likely due to NK and T effector cell functions upon engagement with the inhibitory NK
      receptor CD94/NKG2A. However, our recent results on an enlarger cohort of patients suggest
      that if this observation holds true for MSS CRC, HLA-E over-expression is inversely
      associated with a good prognosis in MSI CRC. Thus, the phenotype and function of TIL,
      depending on the MSI/MSS status of CRC have to be precised. The investigators hypothesized
      that in MSI CRC, known to express a high number of MSI-H related frameshift peptides which
      represent a pool of tumor specific antigens, HLA-E could present peptides to TCR of non
      conventional CD8+ HLA-E-restricted alpha-betaT cells (also expressing CD94), then inducing a
      strong antitumor cytolytic activity. Therefore, the aim of this project is to determine the
      exact phenotype, function and specificity of the CD94+ TIL in CRC, depending on both the
      HLA-E and the MSI/MSS status of tumor cells. These results could impact the clinical practice
      as anti-NKG2A monoclonal antibodies or frameshift peptide based immunotherapy that could be
      promising new therapeutic options in CRC patients.
observational model: Cohort
time perspective: Prospective
measure: The phenotype of TIL will be precised by immunohistochemisry and flow cytometry using various combinations of monoclonal antibodies to identify different subset of TIL and their frequency, especially those expressing NKG2A or NKG2C chain.
time frame: Until 5 years
arm group label: Group "patients with colorectal cancer"
description: Major patients treated surgically for colorectal cancer at Nantes University Hospital or at the Institut de Cancerologie de l'Ouest and agreeing to participate in the study
intervention type: Other
intervention name: Non interventional study
arm group label: Group "patients with colorectal cancer"
20 mL of Blood, a tumor fragment and a fragment of colonic mucosa
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: 85 Years
healthy volunteers: No
last name: Céline BOSSARD, Pr
role: Principal Investigator
affiliation: Nantes University Hospital
facility: 
country: France
responsible party type: Sponsor
mesh term: Colorectal Neoplasms
sharing ipd: No