The DOI matches its Crossref record; 74 of the 74 references it cites were found in a registry or an index.
Intratumor depletion of CD4+ cells unmasks tumor immunogenicity leading to the rejection of late-stage tumors
Open accessAbstract
Tumor environment can be critical for preventing the immunological destruction of antigenic tumors. We have observed a selective accumulation of CD4+CD25+ T cells inside tumors. In a murine fibrosarcoma Ld-expressing Ag104, these cells made up the majority of tumor-infiltrating lymphocytes at the late stage of tumor progression, and their depletion during the effector phase, rather than priming phase, successfully enhanced antitumor immunity. We show here that CD4+CD25+ T cells suppressed the proliferation and interferon-γ production of CD8+ T cells in vivo at the local tumor site. Blockade of the effects of IL-10 and TGF-β partially reversed the suppression imposed by the CD4+ cells. Furthermore, local depletion of CD4+ cells inside the tumor resulted in a change of cytokine milieu and led to the eradication of well-established highly aggressive tumors and the development of long-term antitumor memory. Therefore, CD4+CD25+ T cells maintained an environment in the tumor that concealed the immunogenicity of tumor cells to permit progressive growth of antigenic tumors. Our study illustrates that the suppression of antitumor immunity by regulatory T cells occurs predominantly at the tumor site, and that local reversal of suppression, even at a late stage of tumor development, can be an effective treatment for well-established cancers.
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Cites
PD-1 and PD-L1 Immune Checkpoint Blockade to Treat Breast Cancer
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Foxp3 programs the development and function of CD4+CD25+ regulatory T cells
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Cited by
Spranger, S., Dai, D., Horton, B., & Gajewski, T. F. (2017) · Cancer Cell · doi:10.1016/j.ccell.2017.04.003 · Cited by 1,441
Suppression of Antitumor Immunity by Stromal Cells Expressing Fibroblast Activation Protein–α
Kraman, M., Bambrough, P. J., Arnold, J. N., Roberts, E. W., Magiera, L., Jones, J. O., Gopinathan, A., Tuveson, D. A., & Fearon, D. T. (2010) · Science · doi:10.1126/science.1195300 · Cited by 1,134
Regulatory T cells in tumor immunity
Nishikawa, H., & Sakaguchi, S. (2010) · International Journal of Cancer · doi:10.1002/ijc.25429 · Cited by 944
Central Role of Defective Interleukin-2 Production in the Triggering of Islet Autoimmune Destruction
Tang, Q., Adams, J. Y., Penaranda, C., Melli, K., Piaggio, E., Sgouroudis, E., Piccirillo, C. A., Salomon, B. L., & Bluestone, J. A. (2008) · Immunity · doi:10.1016/j.immuni.2008.03.016 · Cited by 729
Quezada, S. A. (2006) · Journal of Clinical Investigation · doi:10.1172/jci27745 · Cited by 700
Metadata
- Authors
- Yu, P., Lee, Y., Liu, W., Krausz, T., Chong, A., Schreiber, H., & Fu, Y.-X.
- Venue
- The Journal of Experimental Medicine
- Publisher
- Rockefeller University Press
- Published
- 2005-03-07
- Volume
- 201
- Issue
- 5
- Pages
- 779-791
- ISSN
- 0022-1007 (ISSN-L)
- 1540-9538
- OpenAlex
- W2132207502
- Cited by
- 432
- References
- 74
- FWCI
- 16.85
- Type
- journal article
- Language
- en
- Open access
- green
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- Yu, P., Lee, Y., Liu, W., Krausz, T., Chong, A., Schreiber, H., & Fu, Y.-X. (2005). Intratumor depletion of CD4+ cells unmasks tumor immunogenicity leading to the rejection of late-stage tumors. The Journal of Experimental Medicine. https://doi.org/10.1084/jem.20041684
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