Immunophenotyping of Stage III Melanoma Reveals Parameters Associated with Patient Prognosis

Nicolas Jacquelot (1, 2) , Maria Paula Roberti (3, 1) , David P. Enot (4, 1) , Sylvie Rusakiewicz (1, 3) , Michaela Semeraro (5, 1) , Sarah Jégou (6) , Camila Flores (1) , Lieping Chen (7) , Byoung S. Kwon (8, 9) , Christophe Borg (10, 11) , Benjamin Weide (12) , François Aubin (10) , Stéphane Dalle (13) , Holbrook Kohrt (14) , Maha Ayyoub (1, 2, 3) , Guido Kroemer (15, 16, 17, 6, 18, 4) , Aurélien Marabelle (1, 3) , Andréa Cavalcanti (19) , Alexander Eggermont (1) , Laurence Zitvogel (1, 2, 3)

1 UMR 1015 - Immunologie des tumeurs et immunothérapie
2 Université Paris-Saclay
3 CIC 1428 , CBT 507 - Centre d'Investigation Clinique en Biotherapie des cancers
4 Plateforme de métabolomique
5 Hôpital Necker - Enfants Malades [AP-HP]
6 UPMC - Université Pierre et Marie Curie - Paris 6
7 Yale University [New Haven]
8 National Cancer Center Korea
9 Tulane University
10 CHRU Besançon - Centre Hospitalier Régional Universitaire de Besançon
11 Inserm CIC 1431 - Centre d'Investigation Clinique de Besançon
12 Eberhard Karls Universität Tübingen = Eberhard Karls University of Tuebingen
13 HCL - Hospices Civils de Lyon
14 Stanford School of Medicine [Stanford]
15 CRC - Centre de Recherche des Cordeliers
16 Equipe labellisée Ligue contre le cancer - CRC - Inserm U1138 - Apoptose, cancer et immunité
17 UPD5 - Université Paris Descartes - Paris 5
18 HEGP - Hôpital Européen Georges Pompidou [APHP]
19 IGR - Institut Gustave Roussy

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 þ CD4 þ and CD3 e CD56 e tumor-infiltrated lymphocytes appear to be independent prognostic factors of short progression-free survival. High NKG2D expression on CD8 þ 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.

Domaines: Médecine humaine et pathologie

Nicolas Jacquelot, Maria Paula Roberti, David P. Enot, Sylvie Rusakiewicz, Michaela Semeraro, et al.. Immunophenotyping of Stage III Melanoma Reveals Parameters Associated with Patient Prognosis. Journal of Investigative Dermatology, 2016, 136 (5), pp.994-1001. ⟨10.1016/j.jid.2015.12.042⟩. ⟨hal-01305495⟩