%0 Journal Article
%T Adoptive TIL Transfer in the Adjuvant Setting for Melanoma: Long-Term Patient Survival
%A Amir Khammari
%A Anne-Chantal Knol
%A Jean-Michel Nguyen
%A C¨¦line Bossard
%A Marc-Guillaume Denis
%A Marie-Christine Pandolfino
%A Ga£¿lle Qu¨¦reux
%A Sylvain Bercegeay
%A Brigitte Dr¨¦no
%J Journal of Immunology Research
%D 2014
%R 10.1155/2014/186212
%X 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 ( ) or OS ( ). 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. 1. Introduction Therapeutic strategies for melanoma targeting the immune system gave rise to a high medical interest over the last decade. Since the first use of interferon and interleukin-2 (IL-2), two unspecific modulating agents, the intensive emphasis on immunological approaches has recently been awarded by approval of the first immunotherapeutic agent, the human monoclonal anti-CTLA-4 (Ipilimumab) antibody, for advanced metastatic stage disease by the FDA and European health agency [1]. In the field of immunotherapy, one of the main melanoma treatments is based on the adoptive transfer of T cells, relying on the use of either specific T cells (in vitro simply selected and amplified or engineered by transduction of high-affinity T-cell receptors or chimeric antigen receptors) or tumor-infiltrating lymphocytes (TIL). The main rationale for this approach is that melanomas are frequently infiltrated by cytotoxic and cytokine-producing CD8+ T cells recognizing autologous tumor-associated antigens (TAA) [2]. Rosenberg¡¯s group first described the adoptive cell transfer-based immunotherapy in humans in 1988 [3] using bulk cultures of lymphocytes derived from autologous melanoma tumors, infused together with high doses of IL-2 in metastatic melanoma patients. After this first trial, TIL transfers have been developed and improved
%U http://www.hindawi.com/journals/jir/2014/186212/