title: Metastatic Lung Lesions as a Preferred Resection Site for Immunotherapy With Tumor Infiltrating Lymphocytes.
abstract: Adoptive cell therapy with tumor infiltrating lymphocytes (TIL) yields 50% response rates in metastatic melanoma and shows promising clinical results in other solid tumors. Autologous TIL cultures are isolated from resected tumor tissue, expanded ex vivo to large numbers and reinfused to the preconditioned patient. In this prospective study, we validate the origin of the tumor biopsy and its effect on T-cell function and clinical response. One hundred forty-four patients underwent surgery and 79 patients were treated with TIL adoptive cell therapy. Cultures from lung tissue were compared with other origins. The success rate of establishing TIL culture from lung tissue was significantly higher compared with nonlung tissue (94% vs. 72%, respectively, P≤0.003). Lung-derived TIL cultures gave rise to higher cell numbers (P≤0.011) and exhibited increased in vitro antitumor reactivity. The average fold expansion for lung-derived TIL during a rapid expansion procedure was 1349±557 compared with 1061±473 for nonlung TIL (P≤0.038). Patients treated with TIL cultures of lung origin (compared with nonlung) had prolonged median overall survival (29 vs. 9.5 mo; P≤0.065). Given the remarkable advancement in minimally invasive thoracic surgery and the results of this study, we suggest efforts should be taken to resect lung metastasis rather than other sites to generate TIL cultures for clinical use.
authors.affiliation: Departments of *Thoracic Surgery †Ella Lemelbaum Institute of Melanoma ‡General and Bariatric Surgery, Sheba Medical Center, Tel Hashomer §Department of Clinical Microbiology and Immunology, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Ronny
authors.initials: R
authors.lastname: Ben-Avi
authors.forename: Orit
authors.initials: O
authors.lastname: Itzhaki
authors.forename: David
authors.initials: D
authors.lastname: Simansky
authors.forename: Dov
authors.initials: D
authors.lastname: Zippel
authors.forename: Gal
authors.initials: G
authors.lastname: Markel
authors.forename: Alon
authors.initials: A
authors.lastname: Ben Nun
authors.forename: Jacob
authors.initials: J
authors.lastname: Schachter
authors.forename: Michal J
authors.initials: MJ
authors.lastname: Besser
mesh_terms: D001706:Biopsy; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D049109:Cell Proliferation; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000379:methods*; D008175:Lung Neoplasms / Q000556:secondary / Q000601:surgery* / Q000628:therapy*; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology* / Q000637:transplantation; D008545:Melanoma / Q000473:pathology / Q000601:surgery / Q000628:therapy*; D009367:Neoplasm Staging; D011013:Pneumonectomy; D011446:Prospective Studies; D016019:Survival Analysis; D016896:Treatment Outcome