title: Tumor infiltrating lymphocyte therapy for metastatic melanoma: analysis of tumors resected for TIL.
abstract: Adoptive cell transfer of tumor-infiltrating lymphocytes (TILs) can mediate objective tumor regression in 49% to 72% of patients with many long-term durable responses. To undergo treatment a patient must have (1) a resectable tumor from which (2) TIL can be generated that (3) exhibit tumor-specific reactivity. From July 2002 to July 2007, 787 tumors from 402 patients were processed for possible use in the generation of TIL, leading to the eventual treatment of 107 patients (27%). Viable TILs were generated in 376 patients (94%), and active, specific TILs were identified in 269 patients (67%). Patient demographics and tumor characteristics were analyzed for possible prognostic factors for growth and activity. Gastrointestinal-derived TIL grew less frequently, whereas lymph node and lung-derived TIL exhibited specific activity more often. TIL that grew and exhibited specific reactivity were from tumors that were larger in diameter and digests that had a higher percentage of lymphocytes. Despite these considerations, active, specific TIL could be generated from almost any site of metastasis. As more centers begin exploring the use of adoptive transfer with TIL, this compendium may provide a framework for therapeutic decision making and future investigation.
authors.affiliation: Surgery Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-1201, USA. slgoffmd@gmail.com
authors.forename: Stephanie L
authors.initials: SL
authors.lastname: Goff
authors.forename: Franz O
authors.initials: FO
authors.lastname: Smith
authors.forename: Jacob A
authors.initials: JA
authors.lastname: Klapper
authors.forename: Richard
authors.initials: R
authors.lastname: Sherry
authors.forename: John R
authors.initials: JR
authors.lastname: Wunderlich
authors.forename: Seth M
authors.initials: SM
authors.lastname: Steinberg
authors.forename: Donald
authors.initials: D
authors.lastname: White
authors.forename: Steven A
authors.initials: SA
authors.lastname: Rosenberg
authors.forename: Mark E
authors.initials: ME
authors.lastname: Dudley
authors.forename: James C
authors.initials: JC
authors.lastname: Yang
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000951:Antigens, Neoplasm / Q000276:immunology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005260:Female; D005770:Gastrointestinal Neoplasms / Q000276:immunology / Q000556:secondary / Q000601:surgery / Q000628:therapy*; D015234:HLA-A Antigens / Q000378:metabolism; D015789:HLA-A2 Antigen; D006801:Humans; D016219:Immunotherapy, Adoptive; D007371:Interferon-gamma / Q000378:metabolism; D008175:Lung Neoplasms / Q000276:immunology / Q000556:secondary / Q000601:surgery / Q000628:therapy*; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology / Q000378:metabolism* / Q000473:pathology / Q000637:transplantation; D008297:Male; D008545:Melanoma / Q000276:immunology / Q000556:secondary / Q000601:surgery / Q000628:therapy*; D008875:Middle Aged; D012074:Remission Induction
chemical_list: D000951:Antigens, Neoplasm; D015234:HLA-A Antigens; C435939:HLA-A*02:01 antigen; D015789:HLA-A2 Antigen; D007371:Interferon-gamma