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PMID: 26829031 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Immunophenotyping of Stage III Melanoma Reveals Parameters Associated with Patient Prognosis.

The Journal of investigative dermatology ·Vol. 136 ·No. 5 ·2016-00-00 ·Pages 994-1001

Jacquelot N, Roberti MP, Enot DP, Rusakiewicz S, Semeraro M, Jégou S, Flores C, Chen L, Kwon BS, Borg C, Weide B, Aubin F, Dalle S, Kohrt H, Ayyoub M, Kroemer G, Marabelle A, Cavalcanti A, Eggermont A, Zitvogel L

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.

MeSH Terms
Adult Cohort Studies Combined Modality Therapy Disease-Free Survival Female Humans Immunophenotyping Immunotherapy/methods Lymph Nodes/pathology Male Melanoma/mortality,pathology,therapy Middle Aged Neoadjuvant Therapy/methods Neoplasm Invasiveness/pathology Neoplasm Recurrence, Local/mortality,prevention & control Prognosis Prospective Studies Risk Assessment Skin Neoplasms/mortality,pathology,therapy Survival Analysis
Authors & Affiliations
20 authors, click to expand affiliations / ORCID
Jacquelot Nicolas
INSERM U1015, Gustave Roussy Cancer Center, Villejuif, France; University Paris Saclay, Kremlin Bicêtre, France; Gustave Roussy Cancer Center, Villejuif, France.
Roberti María Paula
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.
Enot David P
Gustave Roussy Cancer Center, Villejuif, France; Metabolomics and Cell Biology Platforms, Gustave Roussy Cancer Center, Villejuif, France.
Rusakiewicz Sylvie
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.
Semeraro Michaela
INSERM U1015, Gustave Roussy Cancer Center, Villejuif, France; Gustave Roussy Cancer Center, Villejuif, France; Center of Clinical Investigation, Hôpital Necker Enfants Malades, Paris, France.
Jégou Sarah
Saint Antoine Hospital, INSERM ERL 1157-CNRS UMR 7203, Paris, France.
Flores Camila
Gustave Roussy Cancer Center, Villejuif, France.
Chen Lieping
Department of Immunobiology, Yale School of Medicine, New Haven, Connecticut, USA.
Kwon Byoung S
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.
Borg Christophe
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.
Weide Benjamin
Division of Dermatooncology, Department of Dermatology, University Medical Center Tübingen, Tübingen, Germany.
Aubin François
Université de Franche Comté, Service de Dermatologie, Centre Hospitalier Universitaire (CHU), Besançon, France.
Dalle Stéphane
Centre Hospitalier Lyon-Sud, Hospices Civils de Lyon and University Claude Bernard Lyon 1, Lyon, France.
Kohrt Holbrook
Division of Oncology, Department of Medicine, Stanford University, Stanford, California, USA.
Ayyoub Maha
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.
Kroemer Guido
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.
Marabelle Aurélien
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.
Cavalcanti Andréa
Gustave Roussy Cancer Center, Villejuif, France; Department of Surgery, Gustave Roussy Cancer Center, Villejuif, France; Department of Dermatology, Gustave Roussy Cancer Center, Villejuif, France.
Eggermont Alexander
Gustave Roussy Cancer Center, Villejuif, France.
Zitvogel Laurence
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.
Supplementary Concepts
Melanoma, Cutaneous Malignant (Disease)
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Article Info
Journal
The Journal of investigative dermatology
Abbr.
J Invest Dermatol
ISSN
1523-1747
DOI
10.1016/j.jid.2015.12.042
Email
laurence.zitvogel@gustaveroussy.fr
Published
2016-00-00
Epub
2016-00-29
Pages
994-1001
Language
English
Region
United States
NLM ID
0426720
PMCID
PMC6156792
Subset
IM
Grants
NCI NIH HHS · P30 CA016359 · United States
NCI NIH HHS · P50 CA121974 · United States
NCI NIH HHS · R01 CA142779 · United States
External Links
PubMed source DOI: 10.1016/j.jid.2015.12.042 PMC Full Text View journal details
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