Fc-dependent depletion of tumor-infiltrating regulatory t cells co-defines the efficacy of anti-CTLA-4 therapy against melanoma Journal Article
| Authors: | Simpson, T. R.; Li, F.; Montalvo Ortiz, W.; Sepulveda, M. A.; Bergerhoff, K.; Arce, F.; Roddie, C.; Henry, J. Y.; Yagita, H.; Wolchok, J. D.; Peggs, K. S.; Ravetch, J. V.; Allison, J. P.; Quezada, S. A. |
| Article Title: | Fc-dependent depletion of tumor-infiltrating regulatory t cells co-defines the efficacy of anti-CTLA-4 therapy against melanoma |
| Abstract: | Treatment with monoclonal antibody specific for cytotoxic T lymphocyte-associated antigen 4 (CTLA-4), an inhibitory receptor expressed by T lymphocytes, has emerged as an effective therapy for the treatment of metastatic melanoma. Although subject to debate, current models favor a mechanism of activity involving blockade of the inhibitory activity of CTLA-4 on both effector (T eff) and regulatory (T reg) T cells, resulting in enhanced antitumor effector T cell activity capable of inducing tumor regression. We demonstrate, however, that the activity of anti-CTLA-4 antibody on the T reg cell compartment is mediated via selective depletion of T reg cells within tumor lesions. Importantly, T reg cell depletion is dependent on the presence of Fc? receptor-expressing macrophages within the tumor microenvironment, indicating that T reg cells are depleted in trans in a contextdependent manner. Our results reveal further mechanistic insight into the activity of anti-CTLA-4-based cancer immunotherapy, and illustrate the importance of specific features of the local tumor environment on the final outcome of antibody-based immunomodulatory therapies © 2013 Simpson et al. |
| Journal Title: | Journal of Experimental Medicine |
| Volume: | 210 |
| Issue: | 9 |
| ISSN: | 0022-1007 |
| Publisher: | Rockefeller University Press |
| Date Published: | 2013-08-26 |
| Start Page: | 1695 |
| End Page: | 1710 |
| Language: | English |
| DOI: | 10.1084/jem.20130579 |
| PROVIDER: | scopus |
| PMCID: | PMC3754863 |
| PUBMED: | 23897981 |
| DOI/URL: | |
| Notes: | --- - Cited By (since 1996):1 - "Export Date: 1 October 2013" - "CODEN: JEMEA" - "Source: Scopus" |
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