| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Department of Pathology, Case Western Reserve University, Cleveland, OH 44106
Proteins involved in class I MHC (MHC-I) Ag processing, such as the TAP, are deficient in some human tumor cells. This suggests that antitumor responses by CD8 T cells provide selection pressure to favor outgrowth of cells with defective processing of tumor Ags. Nonetheless, this evidence is only correlative, and controlled in vivo experiments have been lacking to demonstrate that TAP deficiency promotes survival of tumor cells. To explore the role of Ag processing defects in tumor progression, matched panels of TAP1-positive and TAP1-negative tumor cell lines were generated from a parental transformed murine fibroblast line. Inoculation of C57BL/6 mice with TAP1-negative cells produced large and persistent tumors. In contrast, TAP1-positive cells did not generate lasting tumors, although small tumors were detected transiently and regressed spontaneously. Both TAP1-positive and TAP1-negative cells produced tumors in athymic mice, confirming that TAP-dependent differences in tumorigenicity were due to T cell-dependent immune responses. Inoculation of C57BL/6 mice with mixtures of TAP1-positive and TAP1-negative cells produced tumors composed exclusively of TAP1-negative cells, indicating in vivo selection for cells with TAP deficiency. Thus, loss of TAP function allows some tumor cells to avoid T cell-dependent elimination, resulting in selection for tumor cells with deficient Ag processing.
This article has been cited by other articles:
|
|
 |
|
  S. S. Tykodi, N. Fujii, N. Vigneron, S. M. Lu, J. K. Mito, M. X. Miranda, J. Chou, L. N. Voong, J. A. Thompson, B. M. Sandmaier, et al. C19orf48 Encodes a Minor Histocompatibility Antigen Recognized by CD8+ Cytotoxic T Cells from Renal Cell Carcinoma Patients Clin. Cancer Res., August 15, 2008; 14(16): 5260 - 5269. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Y. Han, M. S. Fletcher, D. L. Urbauer, P. Mueller, C. N. Landen, A. A. Kamat, Y. G. Lin, W. M. Merritt, W. A. Spannuth, M. T. Deavers, et al. HLA Class I Antigen Processing Machinery Component Expression and Intratumoral T-Cell Infiltrate as Independent Prognostic Markers in Ovarian Carcinoma Clin. Cancer Res., June 1, 2008; 14(11): 3372 - 3379. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. F. Setiadi, M. D. David, R. P. Seipp, J. A. Hartikainen, R. Gopaul, and W. A. Jefferies Epigenetic Control of the Immune Escape Mechanisms in Malignant Carcinomas Mol. Cell. Biol., November 15, 2007; 27(22): 7886 - 7894. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Chambers, P. Grufman, V. Fredriksson, K. Andersson, M. Roseboom, S. Laban, M. Camps, E. Z. Wolpert, E. J.H.J. Wiertz, R. Offringa, et al. Induction of Protective CTL Immunity against Peptide Transporter TAP-Deficient Tumors through Dendritic Cell Vaccination Cancer Res., September 15, 2007; 67(18): 8450 - 8455. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Lou, T. Z. Vitalis, G. Basha, B. Cai, S. S. Chen, K. B. Choi, A. P. Jeffries, W. M. Elliott, D. Atkins, B. Seliger, et al. Restoration of the Expression of Transporters Associated with Antigen Processing in Lung Carcinoma Increases Tumor-Specific Immune Responses and Survival Cancer Res., September 1, 2005; 65(17): 7926 - 7933. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. K. Dissanayake, N. Tuera, and S. Ostrand-Rosenberg Presentation of Endogenously Synthesized MHC Class II-Restricted Epitopes by MHC Class II Cancer Vaccines Is Independent of Transporter Associated with Ag Processing and the Proteasome J. Immunol., February 15, 2005; 174(4): 1811 - 1819. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S Krishnakumar, S A Lakshmi, D Abhyankar, and J Biswas Transporter associated protein expression in uveal melanoma Br J Ophthalmol, July 1, 2004; 88(7): 925 - 928. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. E. Ohm, D. I. Gabrilovich, G. D. Sempowski, E. Kisseleva, K. S. Parman, S. Nadaf, and D. P. Carbone VEGF inhibits T-cell development and may contribute to tumor-induced immune suppression Blood, June 15, 2003; 101(12): 4878 - 4886. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. I. Fine, C. D. Han, X. Sun, Y. Liu, and J. A. McCutcheon Tobacco Reduces Membrane HLA Class I That Is Restored by Transfection with Transporter Associated with Antigen Processing 1 cDNA J. Immunol., November 15, 2002; 169(10): 6012 - 6019. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Furukawa, K. Iizuka, J. Poursine-Laurent, N. Shastri, and W. M. Yokoyama A Ligand for the Murine NK Activation Receptor Ly-49D: Activation of Tolerized NK Cells from {beta}2-Microglobulin- Deficient Mice J. Immunol., July 1, 2002; 169(1): 126 - 136. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. H. Igney and P. H. Krammer Immune escape of tumors: apoptosis resistance and tumor counterattack J. Leukoc. Biol., June 1, 2002; 71(6): 907 - 920. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z. Qin, C. Harders, X. Cao, C. Huber, T. Blankenstein, and B. Seliger Increased Tumorigenicity, but Unchanged Immunogenicity, of Transporter for Antigen Presentation 1-deficient Tumors Cancer Res., May 1, 2002; 62(10): 2856 - 2860. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Lankat-Buttgereit and R. Tampe The Transporter Associated With Antigen Processing: Function and Implications in Human Diseases Physiol Rev, January 1, 2002; 82(1): 187 - 204. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. J. de Veer, M. Holko, M. Frevel, E. Walker, S. Der, J. M. Paranjape, R. H. Silverman, and B. R. G. Williams Functional classification of interferon-stimulated genes identified using microarrays J. Leukoc. Biol., June 1, 2001; 69(6): 912 - 920. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. J. Nelson, S. Mukherjee, C. Bundell, S. Fisher, D. van Hagen, and B. Robinson Tumor Progression Despite Efficient Tumor Antigen Cross-Presentation and Effective "Arming" of Tumor Antigen-Specific CTL J. Immunol., May 1, 2001; 166(9): 5557 - 5566. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
