Study of Alterations in Tumor Metabolism Associated With the Development of Immunotherapy Resistance in Melanoma

Study of Alterations in Tumor Metabolism Associated With the Development of Immunotherapy Resistance in Melanoma

Among the mechanisms responsible for resistance to immunotherapy, metabolism seems to play a major role. A better understanding of tumor metabolism appears to be absolutely necessary in order to propose efficient therapeutic alternatives to target tumor cells without exerting a deleterious effect on the cells responsible for the anti-tumor immune response. The main objective is to evaluate metabolism modulations in melanoma cells extracted from metastases of patients sensitive and resistant to immunotherapies (anti-PD1 or anti-PD1+anti-CTLA4).

Inclusion Criteria:

• Female or male, 18 years of age or older
• Stage III unresectable or histologically confirmed stage IV cutaneous melanoma (melanoma of unknown origin is accepted), treatment naïve (metastatic stage) and for which immunotherapy will be started
• Performance Status ≤1
• BRAF status available; BRAF status determination is required but patient will be eligible regardless of BRAF status
• For women of childbearing potential, effective contraception must be initiated during the study.
• Patient affiliated to social security plan
• Patient having signed informed consent

Exclusion Criteria:

• Breastfeeding or pregnant patients: for women of childbearing age, a urine pregnancy test will be performed
• Patients with ocular or mucosal melanoma of metastatic ocular melanoma
• Patients with metastatic melanoma not treated with immunotherapy (i.e. treated with a combination of targeted therapies).
• Contraindication to the initiation of immunotherapy: HIV and/or HCV and/or HBV positive, active autoimmune disease (chronic inflammatory bowel disease such as ulcerative colitis, Crohn's disease, vasculitis, etc.), patients with autoimmune motor neuropathy (such as Guillain Barré syndrome).
• Vulnerable patients: minors, adults under guardianship or curatorship, deprived of liberty
• Vulnerable persons (minors, patients under guardianship or curatorship, deprived of liberty, under court protection, etc.).
• A psychiatric or addiction history that will compromise the patient's ability to consent and follow the proper protocol procedures
• Any other clinical finding that, in the opinion of the principal investigator, could interfere with the results of the study or pose a risk to the patient during the study.