Although immunotherapy revolutionized melanoma outcomes over the last 10 years, only 40-50% of patients respond to treatments and 25% develop acquired resistances. Natural Killer (NK) cells naturally recognize and kill tumor cells. However, the immunosuppressive micro-environment generated by the tumor decreases NK cells' killing activity. CD160 is a NK cell receptor identified and characterized in our laboratory. Engagement of the GPI isoform (CD160-GPI) initiates NK cell cytotoxic response. Upon NK cell activation, a transmembrane isoform (CD160-TM) is neo-synthesized which promotes the amplification of activated NK cell cytotoxicity. The aim of this study is to assess the phenotypic profile of advanced stages melanoma patients' NK cells (mainly CD160-TM expression or its induction) and therefore the therapeutic potential of the use of an anti-CD160-TM agonist antibody to boost the NK-dependent mechanism leading to tumor depletion.
Study Type
OBSERVATIONAL
Enrollment
55
Percentage of effector cells activation and degranulation (CD69 and CD107a staining )
Difference between cells incubated with the anti CD160-TM antibody and with isotipic control ab ( flow cytometry)
Time frame: at inclusion
Overall survival
Time frame: at 1 year post inclusion
Overall survival
Time frame: at 2 years post inclusion
Overall survival
Time frame: at 3 years post inclusion
Overall survival
Time frame: at 4 years post inclusion
Overall survival
Time frame: at 5 years post inclusion
Progression free survival
Time frame: at 1 year
Progression free survival
Time frame: at 2 years
Progression free survival
Time frame: at 3 years
Progression free survival
Time frame: at 4 years
Progression free survival
Time frame: at 5 years
Objective response rate
Time frame: at one year
Objective response rate
Time frame: at 2 years
Objective response rate
Time frame: at 3 years
Objective response rate
Time frame: at 4 years
Objective response rate
Time frame: at 5 years
Phenotypic characteristics of NK cells
Assessment by flow cytometry of the expression levels of activating or inhibitory receptors (e.g. CD160-GPI, NKp46), phenotypic markers (e.g CD16, CD3), as well as activation (CD69) and degranulation (CD107a) markers by the NK cell population (defined as CD3- CD56+ cell). Results will be expressed as the % of positive cells for each marker among the NK cell population
Time frame: at inclusion
cytokine profile
Assessment by flow cytometry using a cytokine beads array (BD Biosciences) of the Th1/Th2/Th17 cytokine content. The presence of the following cytokine will be assessed: IL17-A, IFN-g, TNF, IL10, IL-6, IL-4 and IL-2. The mean fluorescence intensities will be recorded and quantifications will be done, using an individual standard curve, for each cytokine. Results will be expressed in pg/ml.
Time frame: at inclusion
Détection and quantification of sCD160 in patients' serum
Time frame: at inclusion
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