The DOI matches its Crossref record; 40 of the 40 references it cites were found in a registry or an index.
Elucidating the Autoimmune and Antitumor Effector Mechanisms of a Treatment Based on Cytotoxic T Lymphocyte Antigen-4 Blockade in Combination with a B16 Melanoma Vaccine
Open accessAbstract
We have previously shown that small B16 melanomas can be successfully treated using a combination of anti–cytotoxic T lymphocyte antigen (CTLA)-4 monoclonal antibody with a granulocyte/macrophage colony-stimulating factor (GM-CSF) producing irradiated tumor cell vaccine. Regression of tumors results in long-lasting immunity and is frequently accompanied by autoimmune depigmentation. Here we examine the cellular and molecular mechanisms of this combined treatment. Histological examination of depigmented lesions revealed infiltration of polymorphonuclear cells and deposition of antibody. The combination therapy also induced tumor rejection and skin depigmentation in B cell–deficient and in CD4+ T cell–depleted mice. Both effects of the treatment absolutely required CD8+ T cells. Analysis of the response in successfully treated mice revealed elevated levels of CD8+ T cells specific for a nonameric peptide consisting of residues 180–188 of the melanocyte differentiation antigen tyrosinase-related protein (TRP)2. There was no evidence of reactivity to the melanocyte antigens gp100, tyrosinase, Mart1/MelanA, or TRP1. Fas–FasL interactions and perforin played a role in mounting the effector response, whereas the tumor necrosis factor pathway was not required. The cellular requirements for tumor rejection in this therapeutic setting were strikingly different from those in a prophylactic setting. In particular, if mice received a prophylactic vaccine consisting of anti–CTLA-4 and B16–GM-CSF before tumor challenge, full protection was obtained even in the absence of CD8+ T cells. Our data demonstrate that therapeutic autoreactive CD8+ T cell responses can effectively be generated in tumor-bearing mice and stresses the value of studying tumor immunity in a therapeutic rather than a prophylactic setting.
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Citations
Cites
Enhancement of Antitumor Immunity by CTLA-4 Blockade
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T-cell help for cytotoxic T lymphocytes is mediated by CD40–CD40L interactions
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Self-citationA conditioned dendritic cell can be a temporal bridge between a CD4+ T-helper and a T-killer cell
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CD28 and CTLA-4 have opposing effects on the response of T cells to stimulation.
Krummel, M. F., & Allison, J. P. (1995) · The Journal of experimental medicine · doi:10.1084/jem.182.2.459 · Cited by 2,245 · cited 1×
“Generation and purification of anti–CTLA-4 (9H10) has been described previously (17).”
BackgroundSelf-citationHelp for cytotoxic-T-cell responses is mediated by CD40 signalling
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The Central Role of CD4+ T Cells in the Antitumor Immune Response
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Self-citationSutmuller, R. P. M., van Duivenvoorde, L. M., van Elsas, A., Schumacher, T. N. M., Wildenberg, M. E., Allison, J. P., Toes, R. E. M., Offringa, R., & Melief, C. J. M. (2001) · The Journal of Experimental Medicine · doi:10.1084/jem.194.6.823 · Cited by 1,008
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Cited by
Regulatory T cells, tumour immunity and immunotherapy
Zou, W. (2006) · Nature Reviews Immunology · doi:10.1038/nri1806 · Cited by 2,085
Immunosuppressive networks in the tumour environment and their therapeutic relevance
Zou, W. (2005) · Nature Reviews Cancer · doi:10.1038/nrc1586 · Cited by 2,057
Phan, G. Q., Yang, J. C., Sherry, R. M., Hwu, P., Topalian, S. L., Schwartzentruber, D. J., Restifo, N. P., Haworth, L. R., Seipp, C. A., Freezer, L. J., et al. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1533209100 · Cited by 1,575
Self-citationCTLA-4: a moving target in immunotherapy
Rowshanravan, B., Halliday, N., & Sansom, D. M. (2018) · Blood · doi:10.1182/blood-2017-06-741033 · Cited by 1,233
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Metadata
- Authors
- van Elsas, A., Sutmuller, R. P. M., Hurwitz, A. A., Ziskin, J., Villasenor, J., Medema, J.-P., Overwijk, W. W., Restifo, N. P., Melief, C. J. M., Offringa, R., & Allison, J. P.
- Venue
- The Journal of Experimental Medicine
- Publisher
- Rockefeller University Press
- Published
- 2001-08-20
- Volume
- 194
- Issue
- 4
- Pages
- 481-490
- ISSN
- 0022-1007 (ISSN-L)
- 1540-9538
- OpenAlex
- W2105017308
- Cited by
- 309
- References
- 40
- FWCI
- 6.32
- Type
- journal article
- Language
- en
- Open access
- green
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- van Elsas, A., Sutmuller, R. P. M., Hurwitz, A. A., Ziskin, J., Villasenor, J., Medema, J.-P., Overwijk, W. W., Restifo, N. P., Melief, C. J. M., Offringa, R., & Allison, J. P. (2001). Elucidating the Autoimmune and Antitumor Effector Mechanisms of a Treatment Based on Cytotoxic T Lymphocyte Antigen-4 Blockade in Combination with a B16 Melanoma Vaccine. The Journal of Experimental Medicine. https://doi.org/10.1084/jem.194.4.481
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
