title: Immunophenotyping of Stage III Melanoma Reveals Parameters Associated with Patient Prognosis.
abstract: Stage III metastatic melanomas require adequate adjuvant immunotherapy to prevent relapses. Prognostic factors are awaited to optimize the clinical management of these patients. The magnitude of metastatic lymph node invasion and the BRAF(V600) activating mutation have clinical significance. Based on a comprehensive immunophenotyping of 252 parameters per patient in paired blood and metastatic lymph nodes performed in 39 metastatic melanomas, we found that blood markers were as contributive as tumor-infiltrated lymphocyte immunotypes, and parameters associated with lymphocyte exhaustion/suppression showed higher clinical significance than those related to activation or lineage. High frequencies of CD45RA(+)CD4(+) and CD3(-)CD56(-) tumor-infiltrated lymphocytes appear to be independent prognostic factors of short progression-free survival. High NKG2D expression on CD8(+)tumor-infiltrated lymphocytes, low level of regulatory T-cell tumor-infiltrated lymphocytes, and low PD-L1 expression on circulating T cells were retained in the multivariate Cox analysis model to predict prolonged overall survival. Prospective studies are needed to determine whether such immunological markers may guide adjuvant therapies in stage III metastatic melanomas.
authors.affiliation: INSERM U1015, Gustave Roussy Cancer Center, Villejuif, France; University Paris Saclay, Kremlin Bicêtre, France; Gustave Roussy Cancer Center, Villejuif, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Jacquelot
authors.affiliation: INSERM U1015, Gustave Roussy Cancer Center, Villejuif, France; Gustave Roussy Cancer Center, Villejuif, France; CIC Biothérapie IGR Curie CIC1428, Gustave Roussy Cancer Center, Villejuif, France.
authors.forename: María Paula
authors.initials: MP
authors.lastname: Roberti
authors.affiliation: Gustave Roussy Cancer Center, Villejuif, France; Metabolomics and Cell Biology Platforms, Gustave Roussy Cancer Center, Villejuif, France.
authors.forename: David P
authors.initials: DP
authors.lastname: Enot
authors.affiliation: INSERM U1015, Gustave Roussy Cancer Center, Villejuif, France; Gustave Roussy Cancer Center, Villejuif, France; CIC Biothérapie IGR Curie CIC1428, Gustave Roussy Cancer Center, Villejuif, France.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Rusakiewicz
authors.affiliation: INSERM U1015, Gustave Roussy Cancer Center, Villejuif, France; Gustave Roussy Cancer Center, Villejuif, France; Center of Clinical Investigation, Hôpital Necker Enfants Malades, Paris, France.
authors.forename: Michaela
authors.initials: M
authors.lastname: Semeraro
authors.affiliation: Saint Antoine Hospital, INSERM ERL 1157-CNRS UMR 7203, Paris, France.
authors.forename: Sarah
authors.initials: S
authors.lastname: Jégou
authors.affiliation: Gustave Roussy Cancer Center, Villejuif, France.
authors.forename: Camila
authors.initials: C
authors.lastname: Flores
authors.affiliation: Department of Immunobiology, Yale School of Medicine, New Haven, Connecticut, USA.
authors.forename: Lieping
authors.initials: L
authors.lastname: Chen
authors.affiliation: Cancer Immunology Branch, Division of Cancer Biology, National Cancer Center, Ilsan, Goyang, Gyeonggi, Korea; Section of Clinical Immunology, Allergy, and Rheumatology, Department of Medicine, Tulane University Health Sciences Center, New Orleans, Louisiana, USA.
authors.forename: Byoung S
authors.initials: BS
authors.lastname: Kwon
authors.affiliation: Department of Medical Oncology, University Hospital of Besancon, Besancon, France; Clinical Investigational Centre, CIC-1431, University Hospital of Besançon, Besançon, France; INSERM U1098, University of Franche-Comté, Besançon, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Borg
authors.affiliation: Division of Dermatooncology, Department of Dermatology, University Medical Center Tübingen, Tübingen, Germany.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Weide
authors.affiliation: Université de Franche Comté, Service de Dermatologie, Centre Hospitalier Universitaire (CHU), Besançon, France.
authors.forename: François
authors.initials: F
authors.lastname: Aubin
authors.affiliation: Centre Hospitalier Lyon-Sud, Hospices Civils de Lyon and University Claude Bernard Lyon 1, Lyon, France.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Dalle
authors.affiliation: Division of Oncology, Department of Medicine, Stanford University, Stanford, California, USA.
authors.forename: Holbrook
authors.initials: H
authors.lastname: Kohrt
authors.affiliation: INSERM U1015, Gustave Roussy Cancer Center, Villejuif, France; University Paris Saclay, Kremlin Bicêtre, France; Gustave Roussy Cancer Center, Villejuif, France; CIC Biothérapie IGR Curie CIC1428, Gustave Roussy Cancer Center, Villejuif, France.
authors.forename: Maha
authors.initials: M
authors.lastname: Ayyoub
authors.affiliation: Gustave Roussy Cancer Center, Villejuif, France; Metabolomics and Cell Biology Platforms, Gustave Roussy Cancer Center, Villejuif, France; INSERM U1138, Centre de Recherche des Cordeliers, Paris, France; Equipe 11 labellisée par la Ligue contre le Cancer, Centre de Recherche des Cordeliers, Paris, France; Université Paris Descartes, Sorbonne Paris Cité, Paris, France; Université Pierre et Marie Curie, Paris, France; Pôle de Biologie, Hôpital Européen Georges Pompidou, AP-HP, Paris, France.
authors.forename: Guido
authors.initials: G
authors.lastname: Kroemer
authors.affiliation: INSERM U1015, Gustave Roussy Cancer Center, Villejuif, France; Gustave Roussy Cancer Center, Villejuif, France; CIC Biothérapie IGR Curie CIC1428, Gustave Roussy Cancer Center, Villejuif, France.
authors.forename: Aurélien
authors.initials: A
authors.lastname: Marabelle
authors.affiliation: Gustave Roussy Cancer Center, Villejuif, France; Department of Surgery, Gustave Roussy Cancer Center, Villejuif, France; Department of Dermatology, Gustave Roussy Cancer Center, Villejuif, France.
authors.forename: Andréa
authors.initials: A
authors.lastname: Cavalcanti
authors.affiliation: Gustave Roussy Cancer Center, Villejuif, France.
authors.forename: Alexander
authors.initials: A
authors.lastname: Eggermont
authors.affiliation: INSERM U1015, Gustave Roussy Cancer Center, Villejuif, France; University Paris Saclay, Kremlin Bicêtre, France; Gustave Roussy Cancer Center, Villejuif, France; CIC Biothérapie IGR Curie CIC1428, Gustave Roussy Cancer Center, Villejuif, France. Electronic address: laurence.zitvogel@gustaveroussy.fr.
authors.forename: Laurence
authors.initials: L
authors.lastname: Zitvogel
mesh_terms: D000328:Adult; D015331:Cohort Studies; D003131:Combined Modality Therapy; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D016130:Immunophenotyping; D007167:Immunotherapy / Q000379:methods; D008198:Lymph Nodes / Q000473:pathology*; D008297:Male; D008545:Melanoma / Q000401:mortality* / Q000473:pathology* / Q000628:therapy; D008875:Middle Aged; D020360:Neoadjuvant Therapy / Q000379:methods; D009361:Neoplasm Invasiveness / Q000473:pathology; D009364:Neoplasm Recurrence, Local / Q000401:mortality / Q000517:prevention & control*; D011379:Prognosis; D011446:Prospective Studies; D018570:Risk Assessment; D012878:Skin Neoplasms / Q000401:mortality* / Q000473:pathology* / Q000628:therapy; D016019:Survival Analysis; D000096142:Cutaneous Malignant Melanoma
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