Study of Polyfunctionality of Anti-tumor T Lymphocytes in Cancerology: Potential Biomarker for Emerging Immunotherapies

Study Overview
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Brief Summary
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Purposes of this study are : Characterization of polyfunctionality of anti-tumor T lymphocytes using in vitro inhibition of PD-1/PDL-1 pathway Study and comparison of polyfunctionality of anti-tumor T lymphocytes in cohorts of patients with melanoma, lung cancer and renal carcinoma. This cancers are chosen because of use of anti-PD-1 or anti-PDL-1 antibodies Comparison of this technique with IFN-γ Elispot assay for detection and quantification of anti-tumor T lymphocytes after in vitro blockade of PD-1/PDL-1 pathway.

Detailed Description
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In this study an immunomonitoring of specific responses of T lymphocytes to tumor-associated antigens based on detection of intracellular cytokines through flow cytometry, after stimulation with all-tumor antigens and blockade of PD-1/PDL-1 interaction is used. Peripheral blood mononuclear cells of patients with cancers are stimulated with 4 telomerase-peptides or peptides overlapping the entire sequence of survivin. This project studies the frequency and role of polyfunctionality of anti-tumor T lymphocytes in cancerology with an in vitro technique detecting polyfunctional T lymphocytes with a better sensitivity based on removal of an inhibitory PD-1/PDL-1 pathway. It is a flow cytometry protocol with various theoretical advantages in terms of reproducibility and dynamic monitoring of functionality of different sub-populations of polyfunctional anti-tumor T lymphocytes. Moreover, it allows the study of molecular mechanisms involved in proliferation of polyfunctional anti-tumor T lymphocytes with the possibility to sort sub-populations. The use of all-tumor antigens allows the use of this technique to evaluate the presence and prognostic or predictive value of this biomarker in various cancers. Detection of polyfunctional anti-tumor T lymphocytes can be a biomarker of anti-tumor lymphocytic adaptive immunity and a potential eligibility or efficacy criteria for new immunotherapies, such as anti-PD-1 or anti-PDL-1 treatments.

Official Title
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Study of Polyfunctionality of Anti-tumor T Lymphocytes in Cancerology: Potential Biomarker for Emerging Immunotherapies

Conditions
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Cancer

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients affected by melanoma (LyteloMel), lung cancer (TeloCap) or renal carcinoma (EMIR) from cohorts of medical oncology department of CHRU Besançon (France) Exclusion Criteria: -
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Melanoma (LyteloMel)<br> | |
| Lung cancer (TeloCap)<br> | |
| Renal carcinoma (EMIR)<br> | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Polyfunctionality of universal cancer peptides (UCP) and/or survivin-specific responses of T lymphocytes in presence of anti-PDL-1 antibody or isotype control, evaluated with flow cytometry |  | Inclusion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Polyfunctionality of UCP and/or survivin-specific responses of T lymphocytes in each cohort |  | Inclusion | 
| Amplitude of UCP and/or survivin-specific responses of T lymphocytes in presence of anti-PDL-1 antibody or isotype control |  | Inclusion | 
| Amplitude of UCP and/or survivin-specific responses of T lymphocytes evaluated with flow cytometry or IFN-γ Elispot assay |  | Inclusion | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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immune response, T lymphocyte, PD-1/PDL-1 pathway