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J Invest Dermatol. 2016 May;136(5):994-1001. doi: 10.1016/j.jid.2015.12.042. Epub 2016 Jan 29.

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

Author information

1
INSERM U1015, Gustave Roussy Cancer Center, Villejuif, France; University Paris Saclay, Kremlin Bicêtre, France; Gustave Roussy Cancer Center, Villejuif, France.
2
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.
3
Gustave Roussy Cancer Center, Villejuif, France; Metabolomics and Cell Biology Platforms, Gustave Roussy Cancer Center, Villejuif, France.
4
INSERM U1015, Gustave Roussy Cancer Center, Villejuif, France; Gustave Roussy Cancer Center, Villejuif, France; Center of Clinical Investigation, Hôpital Necker Enfants Malades, Paris, France.
5
Saint Antoine Hospital, INSERM ERL 1157-CNRS UMR 7203, Paris, France.
6
Gustave Roussy Cancer Center, Villejuif, France.
7
Department of Immunobiology, Yale School of Medicine, New Haven, Connecticut, USA.
8
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.
9
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.
10
Division of Dermatooncology, Department of Dermatology, University Medical Center Tübingen, Tübingen, Germany.
11
Université de Franche Comté, Service de Dermatologie, Centre Hospitalier Universitaire (CHU), Besançon, France.
12
Centre Hospitalier Lyon-Sud, Hospices Civils de Lyon and University Claude Bernard Lyon 1, Lyon, France.
13
Division of Oncology, Department of Medicine, Stanford University, Stanford, California, USA.
14
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.
15
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.
16
Gustave Roussy Cancer Center, Villejuif, France; Department of Surgery, Gustave Roussy Cancer Center, Villejuif, France; Department of Dermatology, Gustave Roussy Cancer Center, Villejuif, France.
17
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.

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.

PMID:
26829031
DOI:
10.1016/j.jid.2015.12.042
[Indexed for MEDLINE]
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