title: A case of spontaneous systemic immunity to melanoma associated with cure after amputation for extensive regional recurrence.
abstract: OBJECTIVE
  Survival after amputation for melanoma is short; however, rare long-term survivors are reported. The mechanism for durable systemic tumor control in patients with regional failure is not known. To explore whether systemic tumor immunity may be implicated, tumor and circulating immune responses were examined in a patient who survived disease-free 14 years after hip disarticulation.
  
  
  METHODS
  A 71-year-old female with extensive regional metastases of melanoma in the left lower extremity underwent amputation for palliative reasons. Tumor was collected at surgery, and blood was collected during follow-up. Tumor sections were evaluated for lymphocytic infiltration and NY-ESO-1 expression by immunohistochemistry. Cellular immune responses to defined tumor antigens were evaluated by ELISPOT assay, and antibody responses to a panel of tumor antigens were assayed by ELISA.
  
  
  RESULTS
  The patient's tumor had minimal lymphocytic infiltrate (immunotype A). NY-ESO-1 was strongly expressed by the melanoma cells. Circulating T-cell responses to NY-ESO-1 peptides were observed 6 and 12 years postoperatively, and antibodies to NY-ESO-1 were detected 2-6 years after surgery.
  
  
  CONCLUSIONS
  The patient described in this report experienced relentless regional tumor progression, with intravascular metastases, and then 14-year systemic disease-free survival after palliative resection, without evidence of melanoma recurrence before death from other causes. Her immune response to NY-ESO-1 likely failed to control established regional metastases because T cells were unable to infiltrate them. It is possible, however, that among other factors, the host immune response may have contributed to systemic protection.
authors.affiliation: Division of Surgical Oncology, Department of Surgery, University of Virginia, Charlottesville, VA 22908, USA. jmj8e@virginia.edu
authors.forename: Joshua M
authors.initials: JM
authors.lastname: Judge
authors.forename: Louis B
authors.initials: LB
authors.lastname: Brill
authors.forename: Kelly T
authors.initials: KT
authors.lastname: Smith
authors.forename: Donna H
authors.initials: DH
authors.lastname: Deacon
authors.forename: James W
authors.initials: JW
authors.lastname: Patterson
authors.forename: William W
authors.initials: WW
authors.lastname: Grosh
authors.forename: Achim A
authors.initials: AA
authors.lastname: Jungbluth
authors.forename: Sacha
authors.initials: S
authors.lastname: Gnjatic
authors.forename: Craig L
authors.initials: CL
authors.lastname: Slingluff
mesh_terms: D000368:Aged; D000671:Amputation, Surgical / Q000379:methods*; D000951:Antigens, Neoplasm / Q000276:immunology / Q000378:metabolism; D005260:Female; D006801:Humans; D035002:Lower Extremity / Q000601:surgery; D008214:Lymphocytes / Q000276:immunology / Q000378:metabolism; D008545:Melanoma / Q000276:immunology / Q000378:metabolism / Q000601:surgery*; D008565:Membrane Proteins / Q000276:immunology / Q000378:metabolism; D009364:Neoplasm Recurrence, Local / Q000276:immunology / Q000378:metabolism / Q000601:surgery*; D010166:Palliative Care; D012878:Skin Neoplasms / Q000276:immunology / Q000378:metabolism / Q000601:surgery*; D017741:Survivors; D013997:Time Factors
chemical_list: D000951:Antigens, Neoplasm; C104948:CTAG1B protein, human; D008565:Membrane Proteins