title: Adoptive TIL transfer in the adjuvant setting for melanoma: long-term patient survival.
abstract: Two first analyses of our clinical trial on TIL as adjuvant therapy for melanoma were published in 2002 and 2007. We present here an update of the clinical results after a 17-year median followup. In this trial, disease-free patients were randomly assigned to receive either TIL/IL-2 or IL-2. The relapse-free survival (RFS) was the primary objective. Eighty-eight patients were enrolled. A new analysis performed in May 2013 did not show significant changes in RFS or OS duration. However, our first finding on the association between the number of invaded lymph nodes and TIL effectiveness was strengthened. The Cox model adjusted on this interaction showed for the first time a significant treatment effect when considering the overall population, both on the RFS and OS. Patients treated with TIL had a longer RFS (P = 0.023) or OS (P = 0.020). This study being with a very long followup (17 years), confirmed the association between TIL effectiveness and the number of invaded lymph nodes, indicating that a low tumor burden could be a crucial factor enhancing the curative effect of TIL in possible microscopic residual disease. Moreover, we confirmed that a prolonged survival was associated with the presence of specific TIL and a decrease in Foxp3 expression.
authors.affiliation: Skin Cancer Unit, CHU Hôtel-Dieu, 1 Place Alexis Ricordeau, 44093 Nantes, France ; CRCNA, INSERM U892, CNRS 6299, 9 Quai Moncousu, 44093 Nantes, France.
authors.forename: Amir
authors.initials: A
authors.lastname: Khammari
authors.affiliation: CRCNA, INSERM U892, CNRS 6299, 9 Quai Moncousu, 44093 Nantes, France.
authors.forename: Anne-Chantal
authors.initials: AC
authors.lastname: Knol
authors.affiliation: CRCNA, INSERM U892, CNRS 6299, 9 Quai Moncousu, 44093 Nantes, France ; PIMESP-SEB, Hôpital St Jacques, 85 rue St Jacques, 44093 Nantes, France.
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Nguyen
authors.affiliation: Service d'Anatomie et Cytologie Pathologiques, CHU Hôtel-Dieu, 30 boulevard Jean Monnet, 44093 Nantes, France.
authors.forename: Céline
authors.initials: C
authors.lastname: Bossard
authors.affiliation: Plateforme de Génétique des Cancers, CHU Hôtel-Dieu, 1 Place Alexis Ricordeau, 44000 Nantes, France.
authors.forename: Marc-Guillaume
authors.initials: MG
authors.lastname: Denis
authors.affiliation: CRCNA, INSERM U892, CNRS 6299, 9 Quai Moncousu, 44093 Nantes, France ; Unité de Thérapie Cellulaire et Génique (UTCG), CHU Hôtel-Dieu, 9 Quai Moncousu, 44093 Nantes, France.
authors.forename: Marie-Christine
authors.initials: MC
authors.lastname: Pandolfino
authors.affiliation: Skin Cancer Unit, CHU Hôtel-Dieu, 1 Place Alexis Ricordeau, 44093 Nantes, France ; CRCNA, INSERM U892, CNRS 6299, 9 Quai Moncousu, 44093 Nantes, France.
authors.forename: Gaëlle
authors.initials: G
authors.lastname: Quéreux
authors.affiliation: Unité de Thérapie Cellulaire et Génique (UTCG), CHU Hôtel-Dieu, 9 Quai Moncousu, 44093 Nantes, France.
authors.forename: Sylvain
authors.initials: S
authors.lastname: Bercegeay
authors.affiliation: Skin Cancer Unit, CHU Hôtel-Dieu, 1 Place Alexis Ricordeau, 44093 Nantes, France ; CRCNA, INSERM U892, CNRS 6299, 9 Quai Moncousu, 44093 Nantes, France ; Unité de Thérapie Cellulaire et Génique (UTCG), CHU Hôtel-Dieu, 9 Quai Moncousu, 44093 Nantes, France.
authors.forename: Brigitte
authors.initials: B
authors.lastname: Dréno
mesh_terms: D015415:Biomarkers / Q000378:metabolism; D005500:Follow-Up Studies; D006801:Humans; D016130:Immunophenotyping; D016219:Immunotherapy, Adoptive / Q000009:adverse effects; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology* / Q000378:metabolism; D008545:Melanoma / Q000235:genetics / Q000276:immunology* / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D009367:Neoplasm Staging; D010641:Phenotype; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers
references.citation: Clin Cancer Res. 2009 Jan 1;15(1):390-9
references.pmid: 19118070
references.citation: N Engl J Med. 2010 Aug 19;363(8):711-23
references.pmid: 20525992
references.citation: Eur J Immunol. 1990 Apr;20(4):825-31
references.pmid: 1971794
references.citation: Cytotechnology. 2010 Oct;62(5):403-12
references.pmid: 20730489
references.citation: Clin Cancer Res. 2007 Sep 15;13(18 Pt 1):5256-61
references.pmid: 17875753
references.citation: Ophthalmology. 2009 May;116(5):981-989.e1
references.pmid: 19410956
references.citation: J Exp Med. 2008 Oct 27;205(11):2673-82
references.pmid: 18936238
references.citation: Cancer Immunol Immunother. 2002 Nov;51(10):539-46
references.pmid: 12384805
references.citation: Curr Opin Immunol. 2013 Apr;25(2):268-76
references.pmid: 23579075
references.citation: Ann Surg Oncol. 2013 Sep;20(9):3106-11
references.pmid: 23681603
references.citation: PLoS One. 2012;7(12):e48729
references.pmid: 23284620
references.citation: Cancer Immunol Immunother. 2002 Nov;51(10):532-8
references.pmid: 12384804
references.citation: Mol Cell Probes. 2004 Oct;18(5):349-52
references.pmid: 15294323
references.citation: J Immunother (1991). 1991 Dec;10(6):405-11
references.pmid: 1768674
references.citation: J Transl Med. 2011 Nov 28;9:204
references.pmid: 22123319
references.citation: N Engl J Med. 1988 Dec 22;319(25):1676-80
references.pmid: 3264384
references.citation: Cancer Immunol Immunother. 2001 May;50(3):134-40
references.pmid: 11419180
references.citation: Cancer Immunol Immunother. 2007 Nov;56(11):1853-60
references.pmid: 17549472
references.citation: Exp Dermatol. 2011 May;20(5):430-4
references.pmid: 21410773
references.citation: Annu Rev Immunol. 2006;24:175-208
references.pmid: 16551247
references.citation: Cancer J. 2012 Mar-Apr;18(2):160-75
references.pmid: 22453018
references.citation: Cancer Immunol Immunother. 2007 Apr;56(4):515-26
references.pmid: 16874485
references.citation: J Immunol Methods. 1993 Feb 26;159(1-2):197-207
references.pmid: 8445253
references.citation: Eur J Dermatol. 2007 Jul-Aug;17(4):295-301
references.pmid: 17540635
references.citation: Exp Dermatol. 2004 Aug;13(8):484-90
references.pmid: 15265012