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Updated: Aug 23, 2026
Spatial and Temporal Control of Murine Melanoma Initiation from Mutant Melanocyte Stem Cells
Published on: June 7, 2019
Role of TAP-1 and/or TAP-2 antigen presentation defects in tumorigenicity of mouse melanoma
Shefali Agrawal1, Keith Reemtsma, Emilia Bagiella
1Department of Surgery, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA. shefali_agrawal@urmc.rochester.edu
Abstract:
Mutations in transporters associated with antigen processing (TAP-1 and -2) required for the transport of cytosolic endogenous peptides to the endoplasmic reticulum correlate with increased metastatic potential and reduced host survival in several malignancies. To address the possible function of TAP as a "tumor suppressor" gene, we show that correction of TAP-1 and/or TAP-2 defects in B16 mouse melanoma enhanced the cell surface expression of MHC class I molecules and significantly reduced the rate of subcutaneous tumor growth and pulmonary metastatic burden. Cytotoxic assays confirmed increased sensitivity of TAP-1 and/or TAP-2 transfected clones of B16 melanoma to cytotoxic T lymphocytes. These results indicate that the expression of TAP limits the malignant potential of tumors with implications for CD8(+) T cell-based immunotherapy in controlling growth of certain TAP-deficient malignancies.
Insights
Restoring transporters associated with antigen processing (TAP) in melanoma cells reduced tumor growth and metastasis. This suggests TAP acts as a tumor suppressor, enhancing immune responses against cancer.
Area of Science:
- Immunology
- Cancer Biology
- Molecular Biology
Background:
- Mutations in transporters associated with antigen processing (TAP-1 and -2) are linked to increased metastasis and reduced survival in various cancers.
- TAP proteins are crucial for transporting endogenous peptides to the endoplasmic reticulum for MHC class I presentation.
Purpose of the Study:
- To investigate the potential of TAP as a tumor suppressor gene.
- To evaluate the impact of correcting TAP-1 and/or TAP-2 defects in B16 mouse melanoma.
Main Methods:
- Correction of TAP-1 and/or TAP-2 defects in B16 melanoma cells.
- Assessment of MHC class I expression on the cell surface.
- Monitoring of subcutaneous tumor growth and pulmonary metastatic burden.
- Cytotoxic assays using cytotoxic T lymphocytes (CTLs).
Main Results:
- Restoration of TAP-1 and/or TAP-2 enhanced MHC class I expression on B16 melanoma cells.
- Significant reduction in subcutaneous tumor growth and pulmonary metastasis was observed.
- TAP-corrected melanoma cells showed increased sensitivity to CTL-mediated killing.
Conclusions:
- TAP functions as a tumor suppressor gene, limiting malignant potential.
- Restoring TAP expression can enhance anti-tumor immunity, particularly CD8(+) T cell responses.
- Implications for CD8(+) T cell-based immunotherapy in managing TAP-deficient malignancies.
