Analysis of HLA class I expression in progressing and regressing metastatic melanoma lesions after immunotherapy.
Despite the potential efficacy of cancer immunotherapy in preclinical studies, it did not show yet significant positive clinical results in humans with only a small number of cancer patients demonstrating objective tumor regression. This poor clinical outcome can be explained by the generation of sophisticated tumor immune escape mechanism, in particular, abnormalities in the expression of HLA class I antigens. We have studied the expression of HLA class I antigens in ten metastatic lesions obtained from a melanoma patient undergoing immunotherapy. Five lesions were obtained after Interferon-alpha-2b treatment and five after autologous vaccination plus BCG (M-VAX). Eight metastases were regressing after immunotherapy while two were progressing. The eight regressing metastases showed high level of HLA class I expression, whereas the two progressing lesions had low levels as measured by real time PCR and immunohistological techniques. These results indicate a strong association between HLA class I expression and progression or regression of the metastatic lesions. Our data support the hypothesis that the level of HLA class I expression is an important parameter of tumor immune escape that needs to be monitored.
Departamento de Análisis Clínicos, Hospital Universitario Virgen de las Nieves, Avd. Fuerzas Armadas 2, 18014 Granada, Spain.
Rafael
R
Carretero
José M
JM
Romero
Francisco
F
Ruiz-Cabello
Isabel
I
Maleno
Felix
F
Rodriguez
Francisco M
FM
Camacho
Luis M
LM
Real
Federico
F
Garrido
Teresa
T
Cabrera
D019496:Cancer Vaccines / Q000627:therapeutic use*; D018450:Disease Progression; D015395:Histocompatibility Antigens Class I / Q000378:metabolism*; D006801:Humans; D007167:Immunotherapy; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D019656:Loss of Heterozygosity; D008175:Lung Neoplasms / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D008207:Lymphatic Metastasis; D008545:Melanoma / Q000378:metabolism / Q000556:secondary / Q000628:therapy*; D018895:Microsatellite Repeats; D009367:Neoplasm Staging; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014057:Tomography, X-Ray Computed; D019139:Tumor Escape / Q000276:immunology
D019496:Cancer Vaccines; D015395:Histocompatibility Antigens Class I; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D011994:Recombinant Proteins