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.

Inclusion Criteria :

• Patients aged18-years old or over
• ECOG score between 0-2
• Inoperable stage III or stage IV melanoma
• Naïve of treatment or in progression after one or several treatment lines
• Give their written consent for the present study and be included in MelBase cohort.
• health insurance coverage.

Supplementary inclusion criteria for part II :

• skin or subcutaneous melanoma lesions
• agree and inform consent for a cutaneous biopsy or a tumor sample if presenting lymph nodes involvement if part of the usual clinical practice.

Exclusion Criteria:

• Pregnant and breastfeeding women
• Patients with psychiatric disorders
• Patients already included in another clinical trial
• Having received chemotherapy or radiotherapy during the last 4 weeks,
• Patient presenting another solid or blood cancer, chronic viral infection (e.g. HIV, HBV or HCV)
• Been treated with more than 10mg of steroids until the 4 weeks before inclusion.
• Refusal to participate to the study
• Patients under guardianship or curatorship
• Patients on state medical aid

Inoperable stage III/ stage IV melanoma patients