| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Regular Articles |
Reduces Melanosomal Antigen Expression and Recognition of Melanoma Cells by Cytotoxic T Cells
From the Department of Pathology,*
Cardinal BernardinCancer Center, Skin Oncology Research Program, and the CancerImmunology Program,
Loyola University MedicalCenter, Maywood, Illinois; and the SurgeryBranch,
National Institutes of Health,Bethesda Maryland
In malignant melanoma, tumor-infiltrating lymphocytes are
frequently reactive with melanosomal antigens. Achieving complete
remissions by peptide therapy is frequently hampered by metastases
evading immune recognition. The tumor microenvironment seems to favor
reduced expression of target antigens by melanoma cells. Among
candidate factors, interferon-
(IFN-) (102 to
103 U/ml) suppressed expression of antigens MART-1,
TRP-1, and gp100 by M14 melanoma cells as shown by
immunohistology and fluorescence-activated cell sorting
analysis, reducing MART-1 expression by >65%. Northern blot
analysis revealed that reduced expression was regulated at the
transcriptional level, demonstrating a 79% reduction in MART-1
transcript abundance after 32 hours of IFN- treatment. To evaluate
consequences of IFN- exposure for immune recognition,
MART-1-responsive T cells were reacted with pretreated HLA-matched
melanoma cells. Cytotoxicity was reduced up to 78% by IFN-
pretreatment, and was restored by addition of MART-1 peptide
AAGIGILTV for 2 hours. Examination of melanoma lesions by quantitative
reverse transcriptase-polymerase chain reaction revealed up to 188-fold
more abundant IFN- transcripts when compared to control skin. Laser
capture microdissection and immunohistology localized most
IFN--producing T cells to the tumor stroma. Reduced MART-1
expression was frequently observed in adjacent tumor cells.
Consequently, IFN- may enhance inflammatory responses yet
hamper effective recognition of melanoma cells.
This article has been cited by other articles:
 |
|
 |
|
  V. Robila, M. Ostankovitch, M. L. Altrich-VanLith, A. C. Theos, S. Drover, M. S. Marks, N. Restifo, and V. H. Engelhard MHC Class II Presentation of gp100 Epitopes in Melanoma Cells Requires the Function of Conventional Endosomes and Is Influenced by Melanosomes J. Immunol., December 1, 2008; 181(11): 7843 - 7852. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. S. Dunn, T. J. Haggerty, M. Kono, P. J. Durda, D. Butera, D. B. Macdonald, E. M. Benson, L. B. Rose, and J. T. Kurnick Enhancement of Human Melanoma Antigen Expression by IFN-beta J. Immunol., August 15, 2007; 179(4): 2134 - 2142. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Liu, S. J. O'Day, D. Yang, P. Boasberg, R. Milford, T. Kristedja, S. Groshen, and J. Weber Impact of Gene Polymorphisms on Clinical Outcome for Stage IV Melanoma Patients Treated with Biochemotherapy: An Exploratory Study Clin. Cancer Res., February 1, 2005; 11(3): 1237 - 1246. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. J. Dobrzanski, J. B. Reome, J. A. Hollenbaugh, and R. W. Dutton Tc1 and Tc2 Effector Cell Therapy Elicit Long-Term Tumor Immunity by Contrasting Mechanisms That Result in Complementary Endogenous Type 1 Antitumor Responses J. Immunol., February 1, 2004; 172(3): 1380 - 1390. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. G. Carrabba, C. Castelli, M. J. Maeurer, P. Squarcina, A. Cova, L. Pilla, N. Renkvist, G. Parmiani, and L. Rivoltini Suboptimal Activation of CD8+ T Cells by Melanoma-derived Altered Peptide Ligands: Role of Melan-A/MART-1 Optimized Analogues Cancer Res., April 1, 2003; 63(7): 1560 - 1567. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. J. Durda, I. S. Dunn, L. B. Rose, D. Butera, E. M. Benson, F. Pandolfi, and J. T. Kurnick Induction of "Antigen Silencing" in Melanomas by Oncostatin M: Down-Modulation of Melanocyte Antigen Expression Mol. Cancer Res., April 1, 2003; 1(6): 411 - 419. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
