To evaluate the feasibility of adoptive cell therapy (ACT) using ex vivo‐expanded tumor‐infiltrating lymphocytes (TILs) in Japanese patients with melanoma who failed immune‐checkpoint inhibitor therapy, an open‐label, single‐arm, pilot study was conducted.,We investigated the immunological and genetic factors of the pretreatment tumor and expanded TILs that may be associated with the clinical response.,The treatment protocol comprised preparation of TIL culture, lympho‐depleting non‐myeloablative preconditioning with cyclophosphamide and fludarabine, TIL infusion, and intravenous administration of low‐dose IL‐2.,Three patients of clinical subtypes mucosal, superficial spreading, and acral melanoma underwent TIL‐ACT.,Most severe adverse events, including fever and leukopenia, were manageable with the supportive regimen specified in the protocol, suggesting that the TIL‐ACT regimen is suitable for Japanese patients with melanoma.,One patient showed a short‐term partial response, one relatively long‐stable disease, and one experienced disease progression.,Whole‐exome and transcriptional sequencing of isolated tumor cells and immunohistochemical analyses before TIL‐ACT revealed various immunostimulatory factors, including a high tumor mutation burden and immune cell‐recruiting chemokines, as well as various immunosuppressive factors including TGF‐β, VEGF, Wnt/β‐catenin, and MAPK signaling and epithelial‐to‐mesenchymal transition, which might influence the efficacy of TIL‐ACT.,Our results imply mechanisms for the antitumor effect of and resistance to TIL‐ACT.,Further studies of immune‐resistant mechanisms of TIL‐ACT are warranted.,This study is registered with the UMIN Clinical Trial Registry (UMIN 000011431).,Various factors involved in the balance of immunostimulation and immunosuppression are important in the TIL‐ACT response for melanoma patients.
This study aims to explore the efficacy of tumor-infiltrating lymphocytes (TIL) along with interferon-α (IFN-α) to treat stage III malignant melanoma (MM) patients in China.,Between May 2010 and October 2014, 77 patients of stage III MM who underwent surgery were collected in this study.,These patients were divided into two groups: patients who received TIL + IFN-α ± RetroNectin-activated cytokine-induced killer cells (R-CIK) in Arm 1 (n = 27) and IFN-α ± R-CIK in Arm 2 (n = 50) as adjuvant therapy.,The primary endpoints were disease-free survival (DFS) time and DFS rates measured at time points of 1, 2, and 3 years.,The secondary endpoints were overall survival (OS) rates measured at time points of 1, 2, 3, and 5 years as well as OS as evaluated by Kaplan-Meier.,Our results indicated that the median DFS and OS in Arm 1 were significantly better than those in Arm 2.,The data also demonstrated that DFS rate and OS rates in Arm 1 were significantly better than those in Arm 2 at all measured time points.,Patients who undergo surgical excision of stage III MM appear to enjoy prolonged DFS and OS when treated with TIL + IFN-α compared to IFN-α alone.