HLA association with response and toxicity in melanoma patients treated with interleukin 2-based immunotherapy.
Peripheral blood lymphocytes from 146 patients with metastatic melanoma undergoing interleukin 2 (IL-2)-based immunotherapy were characterized for HLA A, B, Cw, DR, DQw, and DRw specificities. Patients had been enrolled into sequential treatment protocols with either IL-2 alone (28) or in combination with tumor-infiltrating lymphocytes (TILs) (86), alpha-interferon (26), lymphokine-activated killer cells (16), radiation therapy (7), cyclophosphamide (3), tumor necrosis factor (1), and interleukin 4 (1) for a total of 168 courses of therapy. HLA phenotype was then correlated with response rate and toxicity to IL-2. We noted: (a) a significant difference in the frequency of A11 (20.5% versus 10.2%; P < 0.05) allele between melanoma patients and the North American Caucasian population; (b) a significantly higher frequency of A11 phenotype among responders (40.5%) than in the melanoma patient population (20.5%; P < 0.01), which was even more obvious among patients responding to TIL therapy (47.4% versus 22.1%; P < 0.05); within TIL patients, responders also had an increased frequency of A19 (42.1% versus 25.6%; P < 0.05); (c) a correlation between the number of TILs received and response rate (P < 0.005); and (d) an association between DR4 haplotype and decreased tolerance to IL-2 among the patients receiving TILs (P = 0.01). These results suggest that, in melanoma patients, some HLA Class I specificities may predict for a greater likelihood of response to IL-2-based therapy, while HLA Class II phenotype correlates with tolerance to the combination of TIL and IL-2 therapy.
Marincola
F M
FM
Surgery Branch, National Cancer Institute, NIH, Bethesda, Maryland 20892.
Venzon
D
D
White
D
D
Rubin
J T
JT
Lotze
M T
MT
Simonis
T B
TB
Balkissoon
J
J
Rosenberg
S A
SA
Parkinson
D R
DR
D004334:Drug Administration Schedule; D006680:HLA Antigens / Q000235:genetics*; D006801:Humans; D007167:Immunotherapy; D007376:Interleukin-2 / Q000009:adverse effects / Q000627:therapeutic use*; D016246:Lymphocytes, Tumor-Infiltrating / Q000637:transplantation*; D008545:Melanoma / Q000276:immunology* / Q000628:therapy*; D010641:Phenotype; D011379:Prognosis; D012074:Remission Induction
D006680:HLA Antigens; D007376:Interleukin-2