The DOI matches its Crossref record; 5 of the 5 references it cites were found in a registry or an index.
OX40 engagement and chemotherapy combination provides potent antitumor immunity with concomitant regulatory T cell apoptosis
Open accessAbstract
Expansion and recruitment of CD4+ Foxp3+ regulatory T (T reg) cells are mechanisms used by growing tumors to evade immune elimination. In addition to expansion of effector T cells, successful therapeutic interventions may require reduction of T reg cells within the tumor microenvironment. We report that the combined use of the alkylating agent cyclophosphamide (CTX) and an agonist antibody targeting the co-stimulatory receptor OX40 (OX86) provides potent antitumor immunity capable of regressing established, poorly immunogenic B16 melanoma tumors. CTX administration resulted in tumor antigen release, which after OX86 treatment significantly enhanced the antitumor T cell response. We demonstrated that T reg cells are an important cellular target of the combination therapy. Paradoxically, the combination therapy led to an expansion of T reg cells in the periphery. In the tumor, however, the combination therapy induced a profound T reg cell depletion that was accompanied by an influx of effector CD8+ T cells leading to a favorable T effector/T reg cell ratio. Closer examination revealed that diminished intratumoral T reg cell levels resulted from hyperactivation and T reg cell–specific apoptosis. Thus, we propose that CTX and OX40 engagement represents a novel and rational chemoimmunotherapy.
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A function for interleukin 2 in Foxp3-expressing regulatory T cells
Fontenot, J. D., Rasmussen, J. P., Gavin, M. A., & Rudensky, A. Y. (2005) · Nature Immunology · doi:10.1038/ni1263 · Cited by 1,819
Quezada, S. A. (2006) · Journal of Clinical Investigation · doi:10.1172/jci27745 · Cited by 700
Clearance of apoptotic and necrotic cells and its immunological consequences
Krysko, D. V., D’Herde, K., & Vandenabeele, P. (2006) · Apoptosis · doi:10.1007/s10495-006-9527-8 · Cited by 316
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Khalil, D. N., Smith, E. L., Brentjens, R. J., & Wolchok, J. D. (2016) · Nature Reviews Clinical Oncology · doi:10.1038/nrclinonc.2016.25 · Cited by 929
Self-citationBalachandran, V. P., Cavnar, M. J., Zeng, S., Bamboat, Z. M., Ocuin, L. M., Obaid, H., Sorenson, E. C., Popow, R., Ariyan, C., Rossi, F., et al. (2011) · Nature Medicine · doi:10.1038/nm.2438 · Cited by 521
Self-citationImmunomodulatory effects of cyclophosphamide and implementations for vaccine design
Sistigu, A., Viaud, S., Chaput, N., Bracci, L., Proietti, E., & Zitvogel, L. (2011) · Seminars in Immunopathology · doi:10.1007/s00281-011-0245-0 · Cited by 305
T cell immunotherapies engage neutrophils to eliminate tumor antigen escape variants
Hirschhorn, D., Budhu, S., Kraehenbuehl, L., Gigoux, M., Schröder, D., Chow, A., Ricca, J. M., Gasmi, B., De Henau, O., Mangarin, L. M. B., et al. (2023) · Cell · doi:10.1016/j.cell.2023.03.007 · Cited by 303
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Metadata
- Authors
- Hirschhorn-Cymerman, D., Rizzuto, G. A., Merghoub, T., Cohen, A. D., Avogadri, F., Lesokhin, A. M., Weinberg, A. D., Wolchok, J. D., & Houghton, A. N.
- Venue
- Journal of Experimental Medicine
- Publisher
- Rockefeller University Press
- Published
- 2009-05-04
- Volume
- 206
- Issue
- 5
- Pages
- 1103-1116
- ISSN
- 0022-1007 (ISSN-L)
- 1540-9538
- OpenAlex
- W2134907223
- Cited by
- 227
- References
- 5
- FWCI
- 7.89
- Type
- journal article
- Language
- en
- Open access
- green
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- Hirschhorn-Cymerman, D., Rizzuto, G. A., Merghoub, T., Cohen, A. D., Avogadri, F., Lesokhin, A. M., Weinberg, A. D., Wolchok, J. D., & Houghton, A. N. (2009). OX40 engagement and chemotherapy combination provides potent antitumor immunity with concomitant regulatory T cell apoptosis. Journal of Experimental Medicine. https://doi.org/10.1084/jem.20082205
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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