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Impact of HLA-E Overexpression by Tumor Cells on the Biology of TIL in Colorectal Cancer (HLA-E CCR)

This study is currently recruiting participants.
Verified November 2016 by Nantes University Hospital
Sponsor:
ClinicalTrials.gov Identifier:
NCT02980146
First Posted: December 2, 2016
Last Update Posted: December 2, 2016
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Collaborator:
U892 INSERM Team 3
Information provided by (Responsible Party):
Nantes University Hospital
  Purpose
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.

Condition Intervention
ColoRectal Cancer Other: Non interventional study

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
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.

Resource links provided by NLM:


Further study details as provided by Nantes University Hospital:

Primary Outcome Measures:
  • 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 ]

Biospecimen Retention:   Samples Without DNA
20 mL of Blood, a tumor fragment and a fragment of colonic mucosa

Estimated Enrollment: 40
Study Start Date: June 2016
Estimated Study Completion Date: June 2017
Estimated Primary Completion Date: June 2017 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
Group "patients with colorectal cancer"
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
Other: Non interventional study

  Eligibility

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 85 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Major patients treated surgically for colorectal cancer at the Nantes University Hospital or the West Institute of Cancerology
Criteria

Inclusion Criteria:

  • Major patients treated surgically for colorectal cancer at the Nantes University Hospital or the West Institute of Cancerology
  • Patients agreeing to participate in the study

Non inclusion Criteria:

  • Age> 85 years
  • Neoadjuvant or immunosuppressive therapy for other pathology
  • Size of the tumor insufficient to carry out all the samples dedicated to the research without constraining the diagnostic step (tumoral sampling at least equal to 1 cm3)
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02980146


Contacts
Contact: Céline BOSSARD, Pr 02 40 08 74 00 Celine.bossard@chu-nantes.fr

Locations
France
Nantes University Hospital Recruiting
Nantes, France, 44093
Contact: Céline BOSSARD, Pr         
Sponsors and Collaborators
Nantes University Hospital
U892 INSERM Team 3
Investigators
Principal Investigator: Céline BOSSARD, Pr Nantes University Hospital
  More Information

Responsible Party: Nantes University Hospital
ClinicalTrials.gov Identifier: NCT02980146     History of Changes
Other Study ID Numbers: RC16_0212
First Submitted: November 21, 2016
First Posted: December 2, 2016
Last Update Posted: December 2, 2016
Last Verified: November 2016
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Additional relevant MeSH terms:
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases