abstract: Immunotherapies targeting co-inhibitory receptors recently open a new promising approach of cancer treatment. Indeed, an objective clinical response was observed after treatment by anti-CTLA-4 and anti-PD-1 in many indications but the treatment still failed in 70 to 80 % of cases treated. Given the adverse effects and the high cost of these therapies, there is a need for the development of biomarkers. This review focus on potential predictive biomarkers. In peripheral blood, high level of Il-2 soluble receptor at baseline and absence of ICOS+ CD4-T lymphocytes induction may be associated with the absence of clinical response for melanoma patients treated by ipilimumab (anti-CTLA-4). PD-L1 - PD-1 ligand- expression on cancer lung adenocarcinoma and melanoma is associated with an improved clinical response to anti-PD-1/PD-L1. Nevertheless, a standardization of the biological assays is needed before a clinical translation. CD8-T cell tumor infiltration seems to be a prerequisite to an optimal clinical response after anti-PD-1/PD-L1 administration. In situ high mutational load is associated with a CD8-T cell infiltration and a higher rate of anti-PD-1 and anti-CTLA-4 response. If we consider a more holistic approach, the role of the gut microbiota in the response to these treatments is now well established in pre-clinical experiments. The universal marker is not identified so far, but the reliable marker should be in the tumor compartment and combining multiples markers could be suitable to predict response in different contexts.
authors.affiliation: Service d'immunologie biologique, plateforme d'immunomonitoring, hôpital européen Georges-Pompidou, AP-HP, Paris, France; Centre de recherche des Cordeliers, INSERM, eq15, UMRS 1138, Paris, France. Electronic address: franck.pages@aphp.fr.
authors.forename: Franck
authors.initials: F
authors.lastname: Pagès
authors.affiliation: Université Paris-Descartes, Sorbonne-Paris-Cité, INSERM U970, Paris, France.
authors.forename: Clémence
authors.initials: C
authors.lastname: Granier
authors.affiliation: Service d'immunologie biologique, plateforme d'immunomonitoring, hôpital européen Georges-Pompidou, AP-HP, Paris, France; Centre de recherche des Cordeliers, INSERM, eq15, UMRS 1138, Paris, France.
authors.forename: Amos
authors.initials: A
authors.lastname: Kirilovsky
authors.affiliation: Service d'immunologie biologique, plateforme d'immunomonitoring, hôpital européen Georges-Pompidou, AP-HP, Paris, France; Centre de recherche des Cordeliers, INSERM, eq15, UMRS 1138, Paris, France.
authors.forename: Carine
authors.initials: C
authors.lastname: Elsissy
authors.affiliation: Service d'immunologie biologique, plateforme d'immunomonitoring, hôpital européen Georges-Pompidou, AP-HP, Paris, France; Université Paris-Descartes, Sorbonne-Paris-Cité, INSERM U970, Paris, France. Electronic address: eric.tartour@aphp.fr.
authors.forename: Eric
authors.initials: E
authors.lastname: Tartour
mesh_terms: D000230:Adenocarcinoma / Q000097:blood; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D060890:B7-H1 Antigen / Q000097:blood; D015415:Biomarkers / Q000097:blood*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D006801:Humans; D056747:Immunomodulation; D007167:Immunotherapy / Q000379:methods*; D007249:Inflammation / Q000097:blood; D000074324:Ipilimumab; D008175:Lung Neoplasms / Q000097:blood / Q000628:therapy; D008213:Lymphocyte Activation; D008545:Melanoma / Q000097:blood / Q000628:therapy; D061026:Programmed Cell Death 1 Receptor / Q000097:blood; D015375:Receptors, Interleukin-2 / Q000097:blood; D059016:Tumor Microenvironment / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D060890:B7-H1 Antigen; D015415:Biomarkers; C423236:CD274 protein, human; D000074324:Ipilimumab; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor; D015375:Receptors, Interleukin-2
keywords: Biomarqueurs; CD8-T cell; Lymphocytes T CD8; Marker; Microenvironnement; Mutations et néoépitopes; PD-L1; Tumoral microenvironment; tumoral