title: Impact of clinical and pathologic features on tumor-infiltrating lymphocyte expansion from surgically excised melanoma metastases for adoptive T-cell therapy.
abstract: OBJECTIVE
  Clinical trials on adoptive T-cell therapy (ACT) using expanded tumor-infiltrating lymphocytes (TIL) have shown response rates of over 50% in refractory melanoma. However, little is known how clinical and pathologic features impact TIL outgrowth isolated from metastatic melanoma tumors.
  
  
  METHODS
  We analyzed the impact of clinical and pathologic features on initial TIL outgrowth in 226 consecutive patients undergoing tumor resection. Successful initial TIL outgrowth was defined as ≥40 million viable lymphocytes harvested from all tumor fragments in a 5-week culture. To normalize for the different size of resected tumors and thus available tumor fragments, we divided the number of expanded TIL by the starting number of tumor fragments (TIL/fragment).
  
  
  RESULTS
  Overall, initial TIL outgrowth was successful in 62% of patients, with patients ≤30 years of age (94%; P = 0.01) and female patients (71% vs. 57% for males; P = 0.04) having the highest rate of success. Systemic therapy 30 days before tumor harvest negatively impacted initial TIL outgrowth compared to patients who never received systemic therapy (47% vs. 71%, P = 0.02). Biochemotherapy within 0 to 60 days of tumor harvest negatively impacted the initial TIL outgrowth with a success rate of only 16% (P < 0.0001).
  
  
  CONCLUSIONS
  Parameters such as age, sex, and the type and timing of prior systemic therapy significantly affect the success rate of the initial TIL outgrowth from tumor fragments for ACT; these parameters may be helpful in selecting patients for melanoma ACT.
authors.affiliation: Department of Melanoma Medical Oncology, The University of Texas, M.D. Anderson Cancer Center, Houston, Texas 77030, USA.
authors.forename: Richard W
authors.initials: RW
authors.lastname: Joseph
authors.forename: Vijay R
authors.initials: VR
authors.lastname: Peddareddigari
authors.forename: Ping
authors.initials: P
authors.lastname: Liu
authors.forename: Priscilla W
authors.initials: PW
authors.lastname: Miller
authors.forename: Willem W
authors.initials: WW
authors.lastname: Overwijk
authors.forename: Nebiyou B
authors.initials: NB
authors.lastname: Bekele
authors.forename: Merrick I
authors.initials: MI
authors.lastname: Ross
authors.forename: Jeffrey E
authors.initials: JE
authors.lastname: Lee
authors.forename: Jeffrey E
authors.initials: JE
authors.lastname: Gershenwald
authors.forename: Anthony
authors.initials: A
authors.lastname: Lucci
authors.forename: Victor G
authors.initials: VG
authors.lastname: Prieto
authors.forename: John D
authors.initials: JD
authors.lastname: McMannis
authors.forename: Nicholas
authors.initials: N
authors.lastname: Papadopoulos
authors.forename: Kevin
authors.initials: K
authors.lastname: Kim
authors.forename: Jade
authors.initials: J
authors.lastname: Homsi
authors.forename: Agop
authors.initials: A
authors.lastname: Bedikian
authors.forename: Wen-Jen
authors.initials: WJ
authors.lastname: Hwu
authors.forename: Patrick
authors.initials: P
authors.lastname: Hwu
authors.forename: Laszlo G
authors.initials: LG
authors.lastname: Radvanyi
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use; D005260:Female; D006801:Humans; D016219:Immunotherapy, Adoptive; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology* / Q000473:pathology / Q000637:transplantation; D008297:Male; D008545:Melanoma / Q000276:immunology* / Q000473:pathology / Q000601:surgery / Q000628:therapy; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents